System and method for delivering a therapy and sensing a biological activity in the mouth

ABSTRACT

Methods, devices, and systems are disclosed for controlled delivery of a therapy, such as a stimulant, to a mouth of a subject via an oral device positioned in a secured configuration in the mouth. At least one of a tongue position stimulator (TST) and tongue position sensor (TSE) is provided, according to certain aspects. According to another aspect, a stimulus is delivered to the mouth and/or tongue via a mouthpiece secured to the subject&#39;s teeth. In another regard, a stimulus is delivered that generates a natural response to eliminate or reduce sleep disorders, such as for example at least one of snoring and obstructive sleep apnea.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 13/649,967 filed on Oct. 11, 2012, incorporated herein byreference in its entirety. U.S. patent application Ser. No. 13/649,967filed on Oct. 11, 2012 is a nonprovisional of U.S. provisional patentapplication Ser. No. 61/603,671 filed on Feb. 27, 2012, incorporatedherein by reference in its entirety, a nonprovisional of U.S.provisional patent application Ser. No. 61/551,927 filed on Oct. 27,2011, incorporated herein by reference in its entirety, and a 35 U.S.C.§ 111(a) continuation-in-part of PCT international application numberPCT/US2012/037392 filed on May 10, 2012, incorporated herein byreference in its entirety. PCT international application numberPCT/US2012/037392 filed on May 10, 2012 is a nonprovisional of U.S.provisional patent application Ser. No. 61/603,671 filed on Feb. 27,2012, incorporated herein by reference in its entirety, and anonprovisional of U.S. provisional patent application Ser. No.61/484,520 filed on May 10, 2011, incorporated herein by reference inits entirety. This application is a nonprovisional of U.S. provisionalpatent application Ser. No. 61/603,671 filed on Feb. 27, 2012,incorporated herein by reference in its entirety. Priority is claimed toeach of the foregoing applications.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

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INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

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NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION

A portion of the material in this patent document is subject tocopyright protection under the copyright laws of the United States andof other countries. The owner of the copyright rights has no objectionto the facsimile reproduction by anyone of the patent document or thepatent disclosure, as it appears in the United States Patent andTrademark Office publicly available file or records, but otherwisereserves all copyright rights whatsoever. The copyright owner does nothereby waive any of its rights to have this patent document maintainedin secrecy, including without limitation its rights pursuant to 37C.F.R. § 1.14.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present disclosure relates to methods, devices, and/or systems fordelivering therapies and sensing biologic activities via oral appliancesin the mouth, in particular for stimulating and sensing tongue activityduring sleep, and including in particular for treating sleep disorderbreathing, including but not limited conditions of obstructive sleepapnea, snoring, or mild sleep apnea.

2. Background and Description of Related Art

Snoring, which is very common among humans, is a noise produced whilebreathing during sleep as a result of certain conditions within thebody. In most cases, snoring results from vibration of the soft palateand uvula. Snoring often involves a displacement of the tongue from itsrest position as well as breathing through the mouth resulting from theabnormal positioning and functioning of the tongue. Snoring can bereduced if the tongue is drawn forward to a more normal position (e.g.,in contact with the anatomical folds or wrinkles (rugae) or the mucosaof the anterior palatal region of the mouth. When in an abnormalposition, the tongue leaves a space for the passage of air between thehard palate and the top of the tongue and over the soft palate. Thepassage of air over the soft palate can cause vibrations which are thesource behind the snoring sound.

While some degree of snoring is tolerable and has no significant adverseconsequence, a common problem is that, on its own, snoring can disturbthe sleep of others near the snoring individual. As a result, snoringcan result in a diminished ability to remain attentive on both theindividual snoring as well as others whose sleep might be adverselyaffected by the snoring party. As a result, even moderate snoring canresult in a reduction in work efficiency and lead to a higher risk ofindustrial and driving accidents.

A more serious sleep disorder can result from symptomatic, repeatedupper airway obstruction during sleep, commonly referred to asObstructive Sleep Apnea (OSA). “Apnea” is a Greek word meaning withoutbreath. Individual suffering from sleep apnea literally stop breathingin their sleep. It is not uncommon for the incidence of apnea events tooccur hundreds of times during the night.

In a given night, the number of involuntary breathing pauses or “apneicevents” could be as high as 20 to 60 or more per hour. These breathingpauses are almost always accompanied by snoring between apnea episodes.Sleep apnea can also be characterized by choking sensations. Ingestionof alcohol and sleeping pills increases the frequency and duration ofbreathing pauses in people with sleep apnea.

30-40% of OSA patients cannot tolerate first-line treatment (such ascontinuous positive airway pressure, CPAP. Accordingly individuals mayconsider other options including oral appliances and surgery. Mandibularrepositioning appliances and surgery can offer benefit for selectedpatients, but such conventional remedies can carry risks such astemporomandibular joint disturbance, changes in dental occlusion, ortooth pain for the former and a wide spectrum of potential complicationsthat includes dysphagia or serious perioperative events includingmyocardial infarction and death in the latter.

The importance of the tongue in OSA and snoring has been recognized for30 years, as evidenced by the numerous attempts designed to prevent thetongue from falling backwards or to move it forward actively orpassively. Oral appliances and multiple tongue-directed surgeries showsome promise, but these remedies carry significant risks and sideeffects, in addition to potential significant bleeding and impairmentsof taste, swallowing, or speech. Because of the limitations of availablepassive treatments, active tongue neuromuscular stimulation techniqueswere attempted to implant wire electrodes, surface stimulatingelectrodes and hypoglossal nerve stimulation.

A number of factors contribute to OSA, including dilator muscleactivation, pharyngeal anatomy, lung volume, arousal threshold, andventilatory control, with the former two playing critical roles for mostindividuals. Upper airway patency relies on pharyngeal dilator muscletone and changes in lung volume that counteract collapsing forces,principally intraluminal negative pressure generated during inspirationand anatomical narrowing of the airway. Individuals with OSA maintainpharyngeal patency with greater dilator muscle tone (principallydemonstrated in the genioglossus muscle, the primary muscle within thetongue) during wakefulness; however, sleep onset results in markeddecreases in muscle tone due to the loss of the wakefulness stimulus, inaddition to decreases in negative pressure reflex activity and lungvolume. The effect of decreased muscle tone is magnified in the presenceof tongue enlargement, an anatomical abnormality often seen in OSA,perhaps related to an increase in fat deposition within the tongue basein individuals with greater body mass index.

Additional risk factors for sleep apnea include a family history ofsleep apnea, excess weight, a large neck, a recessed chin, male gender,abnormalities in the structure of the upper airway, smoking, and alcoholuse. Yet sleep apnea can affect both males and females of all ages,including children and any weight. Sleep apnea disturbs normal sleeppatterns and people with sleep apnea often feel very sleepy during theday and their concentration and daytime performance suffer. Theconsequences of sleep apnea range from annoying to life-threatening.They include symptoms suggesting depression, irritability, sexualdysfunction, learning and memory difficulties, and falling asleep whileat work, on the phone, or driving.

Conventional treatment with oral appliances and tongue-directed surgicalprocedures are based on tongue repositioning and/or size reduction.Novel tongue-directed therapies utilizing direct neuromuscularstimulation and oropharyngeal exercises have demonstrated encouraginginitial results, but these approaches continue to be limited by cost,invasiveness, compliance, and/or limited effectiveness.

Untreated sleep apnea patients are 3 times (or more) likely to haveautomobile accidents. It has been estimated that up to 50 percent ofsleep apnea patients have high blood pressure. It has recently beenshown that sleep apnea contributes to high blood pressure and othercardiovascular disease. Risk for heart attack and stroke may alsoincrease in those with sleep apnea. Sleep apnea is a common disorderthat affects millions of men, women and children and is oftenundiagnosed. It is estimated that at least ten million Americans haveunrecognized sleep apnea

Polysomnography is a test that records a variety of body functionsduring sleep, such as the electrical activity of the brain, eyemovement, muscle activity, heart rate, respiratory effort, air flow, andblood oxygen levels. These tests are used both to diagnose sleep apneaand to determine its severity. The specific therapy for sleep apnea istailored to the individual patient based on medical history, physicalexamination, and the results of polysomnography. Traditionally, atherapy for sleep apnea is tailored to the individual patient based onmedical history, physical examination, and the results ofpolysomnography.

Medications are generally not effective in the treatment of sleep apnea.While oxygen is sometimes used in patients with central apnea caused byheart failure, it is not used to treat obstructive sleep apnea. Some ofthe therapies include the use of Provent®, Breatherite® strip, Oralappliances that advance the mandible, continuous positive airwaypressure (CPAP), or maxillomandibular advancement surgery, etc. However,some therapies may be partially or completely ineffective in addressingboth snoring and/or OSA.

Recently Inspire Medical, Imthera Medical, Apnex Medical and others havebeen exploring ways of stimulating tongue, tongue muscle or nerves thatcontrol the tongue by implanting electrodes in the tongue to deliverelectrical signals for stimulation. However, titrating safe levels ofstimulation that does not disturb sleep for each patient is a challenge.Others have explored ways of stimulating the tongue base by making thepatients wear oral devices. The challenge has been the same.

Given the limitations of current therapies, there is an enormous unmetneed for effective, well-tolerated, safe, and minimally invasive OSAtreatments. There also remains a need for reducing the incidence ofsnoring and/or sleep apena that does not require significant physicaland/or surgical intervention on the patient. In the article, “Impairedswallowing reflex in patients with obstructive sleep apnea syndrome”(CHEST 1999; 116:17-21), Teramoto et al. published their findings thattwenty (20) patients with obstructive sleep apnea also had a compromisedswallowing function due to reduced upper airway muscle functions. Fromthis study, one can conclude that increasing the swallowing frequencyduring sleep could result in increased upper airway muscle functions,and thus potentially reduce or eliminate snoring and obstructive sleepapnea.

In view of the above, there remains a need for an effective, safe, andnoninvasive device, for use by itself or during administration of CPAP.The devices, methods and procedures described herein induce a biologicalresponse within a mouth, such as promoting tongue neuromuscularactivation and anterior tongue displacement to reduce airwayobstruction. Additional variations of methods, devices, and systemsdescribed herein can also increase salivation and reduce or eliminatesnoring and obstructive sleep apnea by one or more of the following:stimulating swallowing, improving muscle tone and increasing frequencyof swallowing.

BRIEF SUMMARY OF THE INVENTION

Stimulation of swallowing can be achieved in several ways: stimulationby taste, stimulation by smell and stimulation by mechanical effect thathelps trigger the swallowing reflex. To achieve stimulation, aninterface to the user is provided that allows for delivery of thestimulus in a beneficial way. Variations of the methods and devices caninclude the use of a stimulation appliance delivers one or more stimulito the nose, tongue, and/or mouth to induce the effects described above.For example, variations of the stimulation appliance can include amouthpiece, mask and/or one or more tubes placed within or in proximityto the mouth or nose.

In the cases of taste and smell stimuli, the stimulation applianceincorporates a reservoir that allows for delivery of the stimulus overthe sleep period. It is important that delivery of the stimulus becontrolled to achieve efficient stimulation of swallowing, withoutcausing habituation or arousing involuntary reflexes, such as gagging.The stimulation appliance comprises means to deliver and regulate thestimulus, such as an infusion pump. Delivery of the stimulus can becontinuous or intermittent. For intermittent delivery the periodsbetween delivery of the stimulus can either be regular or variable.Delivery of stimuli can be regulated by time or by responding tophysiological measurements that are related to the condition beingtreated, such as air flow measured at the nostrils, chest cavitymovement, pulse or brain waves. One or more stimuli can be deliveredsimultaneously or sequentially during a treatment or regimen. Thestimulation appliance can incorporate elements that further enhanceinteraction of the user with the stimulus. The stimulation applianceelements are aimed to encourage interaction of the user with thestimulation appliance, such as, tongue movement, mouth movement andstimulating swallowing. These stimulation appliance elements can bechewable, lickable, or suckable and configured to fit comfortably in theuser's mouth, in proximity to the tongue, such as roller balls, spongesand suckers. The stimulation elements can be smooth or incorporate atexture and have a rigid or soft consistency.

In one variation, the methods and devices described herein are intendedto prevent or reduce habituation as a result of applying the stimulantor stimulus. Habituation could eventually lessen the effect of themethods and devices as the individual's response to the stimulus coulddecrease as a result of repeated application of the stimulus/stimulant.

Accordingly, intermittent delivery of the stimulus/stimulant couldproduce a greater stimulating effect. In some variations, random orapparently/seemingly random, on/off application of thestimulant/stimulus could improve effectiveness of the methods and/ordevices.

The stimulation can be used as a stand-alone therapy or as an adjunct toother sleep disturbance therapies, such as CPAP. For example, a CPAPmask can incorporate a taste or smell stimulation appliance to deliver aregimen that enhances the response to CPAP in users that typically arepoor or moderate responders of the CPAP therapy. Using an aerosol ofliquid may be introduced with humidification or through separate tubing.This can be continuous or intermittent. Additional modification to themask can be made to allow for mouth retainer or oral appliance,connected or separate from the CPAP or BiPAP mask that allows foraerosol or fluid to be released into the mouth either continuously orintermittently. To avoid continuous release and potential forhabituation to the stimulus, release can be timed to respiration, apneaevents or apnea cycles, timed with respirations, respiratory effort,respiratory flow, hypoxia, hypopnea, and or oxygen saturations. Furtherit can be used as a screening device for assessing tongue obstruction.Since several anatomical components can contribute to a person's degreeof obstructive sleep apnea, identifying the causes is paramount indeveloping a treatment. Using taste stimulation as a non invasiveevaluation of the tongue has the potential to better stratify andidentify patients that have tongue obstruction as a significantcomponent of their sleep apnea. This is a functional evaluation givingmore information than just relative tongue size or position. This couldsafely and cost effectively screen for more invasive procedures likesurgery or implants that reposition or stimulate the tongue.

The stimulation can be delivered through a typical mouthpiece or maskmade out of rigid or flexible plastics such acrylic, silicone, EVA, PET,polyethylene, SEBS, polyurethane, polypropylene, PVC material. Thedevice can be manufactured using typical plastics processing methods,such as thermoforming, injection molding, transfer molding, liquidinjection molding, overmolding, and the like. The device can bepreformed using standard plastic processes and custom fit to the user ina secondary processing step. The stimulant is released in a controlledfashion to increase salivation. In one embodiment, a solution of a tastecompound made from Xylitol or saline is placed in the stimulationappliance that comprises a delivery pump. The delivery pump can beprogrammed to deliver solution in a continuous or intermittent fashionduring the sleep cycle. The solution is delivered from the pump to themouthpiece or mask via connecting tubing while the user is asleep asdiscussed below. Alternatively, a miniature pump and reservoir can beincorporated within the mouthpiece or mask. The solution is deliveredduring the sleep period to stimulate swallowing, without causingarousals that awaken the user or elicit an involuntary reflex, such asgagging. For example, the solution can be delivered at rates of (0.01 to0.2 ml/min). The solution is made up of Xylitol with concentration inthe range of 2 to 10 Molar. As a result of the taste compound deliveryregimen, the frequency of apneas in a user diagnosed with sleep apnea isreduced 20-40%. The stimulant could also be combined with a texture, forexample, a dissolvable flavored sponge that draws the tongue because oftaste and tactile sensation. The stimulant could also be a roller, likethe roller discussed below, track ball, or other similar structure. Inany case, a physical stimulant could be used, alone or in combinationwith other stimulants, to draw the tongue into a desired position.

Another variation of the methods and devices includes constant or nearconstant delivery of the stimulant but diluting or adjusting thestimulant so that the response is insufficient to wake the individual.For example, in cases where the stimulant is a taste stimulant, thestimulant can be diluted in a solution where the concentration is heldhigh enough to cause the desired response but low enough to avoid wakingthe patient and is continuously delivered over a period of time.

The methods described herein are intended for treating sleep disorderbreathing in a sleeping individual. In one example the method includesproviding a stimulant that induces at least one natural response withina mouth of the sleeping individual when the stimulant enters the mouth;delivering the stimulant at a location behind one or more teeth in themouth to induce at least one natural response to reduce sleep disorderbreathing and improve the ability of the sleeping individual to maintaina sleep state; and intermittently pausing delivery of the stimulant totemporarily cease inducing the at least one natural response, whereintermittently pausing delivery prevents the stimulant from waking theindividual.

The method can include automatically delivering the stimulant from asupply source while the individual is in a sleep state. The naturalresponse can comprise an activity selected from the group consisting ofsalivation, forward movement of the tongue, repositioning of the tongue,swallowing and a combination thereof. At least one of the activitiesdescribed herein can optionally reduce vibrations of a soft palate oruvula without waking the individual.

The oral appliance can be a mandibular advancement device, a custommolded mouthpiece, a continuous positive airway pressure device, amouthguard, and a retainer.

In some variations, the oral appliance comprises an internal reservoirfluidly coupled to the delivery port, the internal reservoir containingat least a portion of the stimulant, and where the delivery portcomprises a valve, where providing the stimulant comprises opening ofthe valve to dispense the stimulant. Alternatively, or in combination,the device can include an external reservoir containing the stimulant.

The stimulant can also trigger an olfactory response in the individual.Alternatively, or in combination, the devices and methods can include asecond stimulant to trigger an olfactory response in the sleepingindividual.

In some variations, intermittently pausing delivery of the stimulantcomprises pausing the stimulant until a triggering signal restartsdelivery of the stimulant. Additionally, the devices and methods caninclude a dispensing unit in electrical communication with a sensor,where the triggering signal is generated in response to the sensor.

Sensors can include a pressure sensor, an optical sensor, a soundsensor, a movement sensor, an electro-magnetic sensor. In one variation,the sensor is positioned in the mouth and generates a signal based on amovement/position of the tongue, or a position/movement of a jaw.Furthermore, the amount of stimulant delivered can be determined by thetriggering signal. For instance the method and/or device can measure adegree of tongue movement with the sensor and use the triggering signalto determine the amount of stimulant based on the degree of movement.

In another variation, delivering the stimulant and intermittentlypausing delivery of the stimulant are timed with an event selected froma group consisting of respiration, respiratory effect, respiratory flow,hypoxia, hypopnea, oxygen saturation, pausing the stimulant until atriggering signal restarts delivery of the stimulant.

Another variation of the method includes a method for minimizing sleepdisturbances in an individual during a state of sleep. In one example,such a method includes positioning a dispensing unit within a mouth ofthe individual, where the dispensing unit comprises at least one portadjacent to a tongue; providing a supply of a stimulant through the portthat induces a biological response in the mouth of the individual whenthe stimulant contacts an anterior surface of the tongue; controllingdelivery of the stimulant between a delivery phase, in which thestimulant is delivered to the mouth to induce the biological responseand a dwell phase, during which delivery of the stimulant to the mouthis stopped, where controlling delivery of the stimulant permitsperiodically inducing the biological response without waking theindividual.

In another variation, the present disclosure includes an oral device fordispensing a stimulant that produces a biological response within themouth to reduce incidents sleep disorder breathing in an individual.Such a device can include a device body having a dental cavity forremovably nesting with one or more structures within the mouth; adispensing port adjacent to an anterior portion of the dental cavity,such that when the device body is positioned within a mouth the dentalcavity is adjacent to the teeth and the dispensing port is adjacent to aposterior surface of teeth such that the stimulant leaving thedispensing port draws the tongue adjacent or next to the posteriorsurface of the teeth; a fluid reservoir fluidly coupled to thedispensing port being configured to maintain a supply of the stimulant;a valve located in a fluid path between the fluid reservoir and thedispensing port where the valve allows for intermittent dispensing ofthe stimulant through the dispensing port. Regardless of location ofplacement, the valve allows for metering or preferential dispensing ofthe stimulant.

A variation of the oral device can further include a palatial nestingsection adjacent to the dental cavity and configured to nest within anarch of a palate to improve retention of the device body within themouth.

In alternative embodiments, stimulants can be made in the form ofcapsules or films that dissolve over time. The capsule or film may beconfigured such that it gives enough time for the patient to fall asleepbefore the stimulant starts to come out of the capsule. The capsule canbe incorporated into a stimulus appliance that the patient wears, suchas mouthpiece, at night. As the patient falls asleep, the capsule startsto dissolve in the mouth and the taste compound starts to leach out ofthe capsule causing the patient to salivate more.

The capsule may incorporate multiple alternating layers of the tastecompound and tasteless transition layers so that intermittent deliveryof the taste is accomplished as the alternating layers dissolve.

Another variation of an oral device according to the principlesdisclosed herein includes a device for producing a biological responsewithin the mouth to reduce sleep disorder breathing having a device bodyhaving a dental cavity for removably nesting with one or more structureswithin the mouth; and a dispensing surface adjacent to an anteriorportion of the dental cavity, such that when the device body ispositioned within a mouth the dental cavity is adjacent to the teeth andthe dispensing surface is adjacent to a posterior surface of the teeth,where the dispensing surface comprises a supply of a stimulant, wherethe stimulant is releasable from the dispensing surface over a period oftime and draws a tongue adjacent to or next to the posterior surface ofthe teeth. Such a device can include the stimulants described hereinthat are deposited as coatings on or into the dispensing surface via aprocess such as UV-linking, solvent-based deposition, or any suchcommercially available procedure.

Some benefits of the present devices, systems and methods include safetyand comfort, increases muscle tone of the upper airway, the ability todistribute in an over-the-counter fashion; reduced cost as compared tomany of the existing remedies and over-the-counter sleep therapymodalities; ease of use; reversible nature of the produce; non-invasive.Additional benefits include the ability for the tongue to move freelyand to allow for swallowing. Other possible uses for the devices andmethods described herein include treatments for oral hygiene,xerostomia, nocturnal bruxism, and/or nocturnal gastroesophogeal reflux.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 depicts a cross sectional view of the upper respiratory tract ina patient having a blocked airway.

FIGS. 2A and 2B illustrate variations of an oral device that can be usedto induce a biological response within a mouth of an individual toreduce the frequency or prevent snoring and/or sleep apnea.

FIGS. 3A and 3B show phantom views of the oral cavity to illustrateexamples of positioning an oral device within a mouth.

FIG. 3C shows a schematic of taste regions on a tongue.

FIGS. 4A and 4B illustrate a condition immediately prior tocontemporaneous to dispensing a stimulant where an individual issleeping and the tongue is in a retracted position causing restrictionof the airway and inability of air to pass through the upper respiratorytract.

FIG. 4C shows one effect of the disbursed stimulant of FIG. 4A.

FIGS. 5A and 5B illustrate one example of a mandibular advancementdevice (MAD) coupled to one or more sensors.

FIGS. 6A to 6E illustrate additional variations of oral devices for useas described herein.

FIG. 7A illustrates another variation of a dispensing device in whichthe device simply comprises a stimulant tube and a scent tube.

FIG. 7B shows a Constant Positive Airway Pressure (CPAP) device combinedwith the teachings disclosed herein.

FIG. 7C shows yet another variation of a dispensing device in which thedevice comprises a stimulant coupled to a solution so that the stimulantcan be diluted.

FIG. 8A illustrates one example of a fiberoptic pressure sensor for usein a variation of an oral appliance as described herein.

FIGS. 8B and 8C show data from a trial using a variation of a device;FIG. 8B shows a chart for an apnea-hypopnea index (AHI) results forindividuals with mild to moderate OSA, while FIG. 8B presents theapnea-hypopnea index (AHI) results for individuals with severe OSA.

FIG. 9 shows the cTST-TSE system according to one aspect of thedisclosure, with certain components shown schematically for simplicityof illustration.

FIG. 10 shows a graph of certain sensed anterior tongue pressure datarecorded versus time under the experiment of Example 2, and reflects anexample comparing time periods of varied ON/OFF states of therapydelivery.

FIG. 11 also shows another graph of other sensed anterior tonguepressure that was recorded vs. time, also under the experimental studyof Example 2, but according to another example showing a period of OFFdelivery condition only.

FIG. 12 shows another bar graph of frequency of sensed anteriorprotective tongue positioning events (per second) vs. time (consecutivenights over 14 day period), also according to the Example 2 experimentalprotocol, but according to another aspect of the study observing resultsof using the same stimulus delivery rates and intervals on four separatenights throughout the 14 day trial.

FIG. 13 shows a bar graph of the same results featured in FIG. 12, perfrequency of sensed anterior tongue positioning events (per second) vs.time (consecutive nights over the 14 day period, in split-night view),but showing comparison results between the first half and the secondhalf of the nights featured in the graph (i.e. “split night” view oranalysis).

FIG. 14 shows another bar graph of experimental results of Example 2according to frequency of sensed anterior protective tonguerepositioning events (per second) vs. time (consecutive nights over 14day period), but showing results of using a shorter interval than thepilot trial protocol with various rates.

FIG. 15 also shows a bar graph of the same results per frequency ofsensed anterior protective tongue repositioning activity events (persecond) vs. time (consecutive nights over 14 day period) shown in FIG.14, but shows comparison results between the first half and the secondhalf (when available) of the nights in split night analysis.

FIG. 16 also shows a bar graph of frequency of sensed anteriorprotective tongue repositioning activity events (per second) vs. time(consecutive nights over 14 day period) but shows results of anothersub-protocol during continuous flow, with no pauses in delivery ofxylitol, but comparing two different stimulant delivery rates.

FIG. 17 shows an x-y plot of sensed tongue movement to the protectiveanterior position as a function of varying stimulant delivery rates overthe experimental design of Example 2.

FIG. 18 also shows another bar graph reflecting sensed anterior tonguerepositioning events over the 14 days of consecutive treatment atvarious rates and protocols of the Example 2 experiment.

DETAILED DESCRIPTION OF THE INVENTION

The methods, devices and systems described herein reduce or eliminatesnoring and/or episodes of sleep apnea and optionally allow for minimalphysical intervention.

FIG. 1 depicts a cross sectional view of the upper respiratory tract ina patient having a blocked airway 10. As discussed above, snoring occursas a result of vibration of the soft palate 14 and uvula 16 that arelocated at the end of the hard palate 18. As illustrated, the tongue 12is moved from its rest position in a rearward direction causingimpingement of the airway 10 by the rear portion of the tongue 12against the uvula 16. As a result, the blockage prevents air, whetherbreathed through the mouth or nose 20, from passing through the airway10 and ultimately into the throat 24. As shown by arrows 30, theabnormal position of the tongue 12 prevents passage of air in the nasalcavity 22. As noted above, this situation leaves a space for the passageof air between the hard palate and the top of the tongue and over thesoft palate. The passage of air over the soft palate can causevibrations which are the source behind the snoring sound as well ascontribute to sleep apnea.

The devices, methods, and systems described herein can ameliorate orprevent snoring and/or blockage of the airway 10 leading to improvedsleep quality in an individual. Such devices, methods and system deliverone or more stimuli to the sleeping individual to induce a natural orbiological response within the body that lessens snoring and/or opensthe airway to minimize the incidence of apnea. In most variations of thedevices, methods and systems, the stimuli (or the delivery rate of thestimuli) should induce the natural response at an effective level thatdoes not wake the individual. However, alternate variations may includedelivering the stimuli with the intent to wake the individual.

FIG. 2A illustrates one variation of an oral device 100 that can be usedto induce a biological response within a mouth of an individual toreduce the frequency or prevent snoring and/or sleep apnea. In thisvariation, the oral device 100 includes a device body 102 having adental cavity 104 for nesting the device on one or more teeth of theindividual. While the illustrated variation shows the device body 102having a dental cavity 104 that accommodates a number of teeth,variations of the device 100 include a dental cavity 104 that is suitedfor nesting the device 100 on one or more teeth. Alternate variationscan include oral devices 100 that nest directly on the palate, gums, orbeneath the tongue. Accordingly, such variations need not include adental cavity.

The illustrated oral device 100 also includes a dispensing port 106 thatcan be used to deliver a stimulant to the oral cavity, mouth and/ortongue. In this variation, the port 106 is coupled to a supply of thestimulus via a tube 108 that forms a part of a fluid path between thesupply or reservoir of the stimulus and the port 106. The tube 108includes a fitting to allow for coupling to an external reservoir. Asdescribed in further detail below, a valve (shown in FIG. 2B) is locatedbetween the port 106 and the reservoir. The valve allows forintermittent dispensing of the stimulant through the dispensing port106. In some cases a valve is not required. Instead, the device uses apressure differential to drive the stimulant through the port.

FIG. 2B illustrates another variation of an oral device 100 for use asdescribed herein. In this variation the device 100 also includes adispensing port 106 used to deliver a stimulant to the oral cavity,mouth and/or tongue. However, in this variation, the port 106 is coupledto a supply or reservoir 110 that is directly coupled to a body 102 oforal device 100. The reservoir 110 is in fluid communication with theport 106 such that a fluid path is formed therebetween. FIG. 2B alsoshows a valve 112 located adjacent to the port 106 where the valveallows for intermittent dispensing of the stimulant through thedispensing port 106. In alternative variations, the valve can be placedanywhere in or around the lumen or fluid path. This variation of thedevice 100 is a wholly self contained oral device that can rely oninternal circuitry to dispense the stimulant and/or rely on an externalunit (not shown) that can wirelessly transmit a triggering signal to thevalve 112 to dispense the stimulant. The dispensing conditions andfrequency are described below. The variation of the oral device 100shown in FIG. 2B can be disposable after depletion of the stimulus orcan have a second refill valve 114 to permit the user to replenish thestimulant as required.

FIGS. 3A and 3B show phantom views of the oral cavity to illustrate someexamples of positioning one or more oral devices 100 can be placed toproduce the natural response that reduces snoring and/or sleep apnea. Asillustrated, the oral device 100 can be positioned or nested to one ormore teeth 8. In alternate variations, the device 100 can be nested ortemporarily affixed to gums, a palate, or other structure within themouth. FIG. 3A shows nesting of the device 100 on the top front teeth 8while FIG. 3B illustrates nesting of the device 100 on the bottom frontteeth 8. However, alternate devices 100 permits removable nesting of thedevice with one or more structures within the mouth, including the sideteeth, or other structures within the mouth. Additionally, thedispensing port 106 can be positioned anywhere on the device. However,the illustrated variation shows a dispensing port 106 adjacent to ananterior portion of the dental cavity or device body. With thispositioning the dental cavity is adjacent to the teeth. Such positioningallows the dispensing port 106 to deliver the stimulant 122 and draw thetongue 12 to a desired position in the mouth. FIGS. 3A and 3B illustrateoral devices 100 that are coupled to external reservoirs 120 that canoptionally include one or more controllers or other dispensing unit tocontrol the delivery of the stimulant 122 to the device 100. As notedabove, variations of the system include reservoirs that are fabricateddirectly onto a body of the device 100. In such cases, the dispensingunit/controller can be positioned on the device 100 body or can beexternal to the device 100 such that a triggering signal is provided viawired or wireless communication.

In addition to the above, variations of the devices described herein orused in procedures described herein can position one or more portsadjacent to specific taste receptors on the tongue. For example, FIG. 3Cillustrates a schematic view of a tongue to demonstrate the variousregions of taste. Typically, the port 106 is positioned adjacent to the“sweet & salt” taste receptors that are positioned on an apex of thetongue. However, ports can be additionally, or alternatively, positionedto target “sour”, “sweet”, or even bitter taste receptors.

FIGS. 4A and 4B illustrate a condition as described above where anindividual is sleeping and the tongue 12 is in a retracted positioncausing restriction of the airway 10 and inability of air as denoted byarrow 30 to pass through the upper respiratory tract. In this variation,the individual previously inserted a variation of an oral implant 100within the mouth. Again, this variation of the oral implant 100 isnested on one or more teeth 8 of the individual. FIG. 4A shows nestingof the implant 100 on the top teeth while FIG. 4B shows nesting of theimplant 100 on the bottom teeth. Again, additional variations allow fortemporary positioning anywhere that allows for the stimulant to induce anatural or biological response.

The device 100 is coupled to a reservoir 120 containing a supply of thestimulant 122. In one variation, the stimulant is deliveredintermittently. Alternatively, or in combination delivery of thestimulant produces the biological response only when necessary. Thisintermittent delivery reduces the probability of waking the individual.The intermittent delivery also serves to minimize the chances of theindividual becoming desensitized to the stimulant. Delivery of thestimulant can be intermittently paused based on any number ofconditions. For example, delivery or pausing delivery of the stimulantcan be time based, or can be based on sensor feedback as describedbelow. Once delivery of the stimulant occurs, as shown by arrows 32, theport 106 delivers the stimulant to a desired area within the mouth(e.g., a surface of the tongue, underneath the tongue, etc.).

Delivery of the stimulant produces a natural response such assalivation, forward movement of the tongue, repositioning of the tongue,swallowing or a combination thereof.

FIG. 4C illustrates the effect of these natural response induced by thestimulant. As shown, the tongue tends to reposition (as shown by arrow34). Any one of the natural responses or a combination thereof causesopening of the previously constricted airway 10. This natural responsere-establishes airflow as shown by arrows 30 in FIG. 4C. As a result,air can pass through the airway 10 to the lungs.

The biological response, in particular inducing saliva generation in themouth allows for pooling of saliva in the mouth, leading the patient toswallow. The increased frequency of swallowing action increases themuscle tone of the airway muscles. As the patient swallow, the patientstops snoring and the upper airway obstruction clears.

The concepts and features described herein can be employed in any numberof devices. In certain variations, the devices include those devicesthat fit within a mouth of the individual. For example, such oralappliance can include mandibular advancement devices, a continuouspositive airway pressure device, a mouthguard, or a retainer.

FIGS. 5A and 5B illustrate one example of a mandibular advancementdevice (MAD) 140 coupled to one or more sensors. Such sensors caninclude a pressure sensor, an optical sensor, a sound sensor, a movementsensor, an electro-magnetic sensor, or any sensor that can detect acondition requiring delivery of the stimulant. For example, FIG. 5Ashows a number of sensors 142 positioned on an interior of the device140. The sensors can be coupled to a controller 146 (either via awireless or a wired connection) so that the sensor detects apre-determined condition. When the condition is triggered, thecontroller 146 and/or sensor can produce a triggering signal to eitherstart or stop delivery of the stimulant. The sensor can be independentof the device 140 or can be positioned outside of the body. Sensors foruse with the devices and methods described herein can be used togenerate a signal based on a movement or position of the tongue,measuring a degree of tongue movement with the sensor and using thetriggering signal to determine the amount of stimulant based on thedegree of movement. Alternatively, or in combination, a triggeringsignal can be timed with an event such as respiration, rate ofrespiration, a respiratory effect (e.g., wheezing or coughing),respiratory flow, hypoxia, hypopnea, oxygen saturation, etc.

The position or force applied to a MAD can be used as a means to triggerdelivery of the chemoattractant stimulant. Mandibular advancementdevices are used to effectively treat snoring and OSA symptoms. The MADfunctions by maintaining the lower jaw in a prescribed position bycreating forward movement of the lower jaw with respect to the upperjaw. This forward movement also creates space in the airway to relievesymptoms. Conversely, in the absence of the lower jaw constraintrelative to the upper jaw, the potential airway space narrows withconcomitant return of symptoms. This lower jaw motion can correlate tothe sleep state of the patient and therefore can be used as a trigger todeliver the stimulant during periods of sleep when snoring and OSAsymptoms are occurring. Accordingly, a mandibular advancement device canbe configured to sense the relative position or force of the lowercomponent of the MAD with respect to the upper component and theresultant change in position or force used to trigger delivery of thestimulant. Alternatively or in combination, the delivery of stimulantcan be simply activated when a threshold relative motion or force isreached. In another variation, the amount of relative motion or forcecan be used to proportionately adjust the dosing of the stimulant in theperiod that the motion or force is measured.

The device can optionally include design features that have limitedintrusion into the mouth yet able to maximize the surface area of thetongue in contact with the device. For example, a person resting in asupine position will often have increase tongue obstruction due togravity. This is demonstrated by the example of a sleeping person whoimproves or eliminates their snoring by rolling onto their side. Anideal contact with the tongue in the supine position is along the bottomteeth. In this position the tongue is resting on the floor of the mouthand bottom teeth. Delivery of the stimulant onto the lower teeth canincrease the muscle tone of the tongue. This increased tone of thetongue is intended to match to that of a person that does not sufferfrom snoring or obstructive sleep apnea.

The device can have the form similar to that of a retainer that is wornat night on the lower teeth. The retainer can be fitted with a port orports along the lingual side of the lower teeth. The port(s) can beconnected to a reservoir of stimulant discussed herein. Alternativelythe flavored compound can line the retainer along the aspect of theretainer that is along the tongue. By placing the retainer and flavorsalong the lower teeth, towards the back of the lower jaw, mandibulardental arch, there is the additional advantage of stimulating theposterior portion of the tongue. The glossopharyngeal nerve innervatesthat posterior (back) one-third part of the tongue. Along with the Vagusnerve that senses taste from the tongue, position and movement can bemeasured by using a fiber optic sensor. For example, sensorscommercially available from FISO Technologies, Inc. Quebec, Canadasuffice. The sensors have dimensions and mechanical properties thatenable the sensors to be positioned in the mouth to obtain tongueposition and tongue movement information without disrupting the user inan awake or sleep state. The sensor can be positioned in the mouth toobtain information relative to the location of the sensor. More than onesensor can be positioned in the mouth to obtain measurements eithersimultaneously or sequentially. For example a pressure sensor can beincorporated into the mouthpiece as described in the referencedprovisional application. The amount of pressure exerted by the tongue asit moves forward can be monitored on a subject during sleep to obtain abaseline behavior. The tongue movement can be correlated to a sleepstate, thereby, obtaining tongue movement information that relates tothe status of the user. During treatment of snoring and OSA, tonguepressure can be monitored as the regimen of stimulant is delivered. Acorrelation between delivery of stimulant and tongue pressure can bedrawn to establish the effect of stimulant on tongue movement. In turn,tongue movement can be correlated to a sleep state of the user, asdescribed above, to establish a correlation between tongue movement andthe effect of stimulant on the sleep state of the user. In anotherexample, a pressure sensor can be positioned in the space underneath thetongue. The pressure measurement can be correlated to the position andtone of the tongue and to the sleep state of the user. In anotherexample, two or more position sensors can be placed in the mouth andtongue movement can be monitored with respect to the sensors.

FIGS. 6A to 6E illustrate additional variations of oral devices 100 foruse as described herein. FIGS. 6A and 6B illustrate an oral device 100similar to that shown above having a dispensing port 106 that can beused to deliver a stimulant to the oral cavity, mouth and/or tongue. Theport 106 is coupled to a supply of the stimulus via a tube 108 thatforms a part of a fluid path between the supply or reservoir of thestimulus and the port 106. In this variation, the tube 108 includes afitting to allow for coupling to an external reservoir. As described infurther detail below, a valve (not shown in FIG. 6A) can be locatedbetween the port 106 and the reservoir. Alternatively, the valve can bepositioned at the port 106. As noted above, some variations of thedevice do not include a valve. Instead, the device uses a pressuredifferential to drive the stimulant through the port.

FIGS. 6C and 6D illustrate another variation of an oral device 100 wherethe dispensing port 106 includes a roller 128. The roller ball can bereplaced with a sponge or other similar type structure. The stimulationelements (roller, sponge, etc.) can be smooth or incorporate a textureand have a rigid or soft consistency that can be used to deliver astimulant to the oral cavity, mouth and/or tongue. The use of thestimulation elements can optionally eliminate the need for a valve formetering the stimulant.

FIG. 6E illustrates another variation of an oral device 150 for use asdescribed herein. In this example, the oral device 150 is configured tofunction as an upper jaw retainer, with a receptacle 152 for the teeth,and with a reservoir 154 that contains a capsule in the upper hardpalate region 156. The stimulant can include a typical gelatin capsulethat dissolves in water or saliva in about 15 to 30 minutes. This timerange is typical for people to fall asleep. Once the capsule dissolvesthe taste compound inside the capsule starts to leach out of the capsuleinto the patient mouth triggering access salivation. In order to preventthe citrus compound from releasing all at once, the citrus compound canbe in the form of a “hard candy” like form. Alternatively, the reservoir154 can be replaced with a supply line that couples the device 150 to anexternal supply of the stimulant.

In another embodiment of this invention the taste compound could be in acompartment in the mouthpiece or retainer and having a valve. The valvecan be controlled by an electronic switch. The sequence of the releaseof the taste compound can be programmed to be once every few seconds tofew minutes. In another embodiment of this invention the taste compoundis in a compartment in the mouthpiece or a retainer and has anelectronically controlled valve. In addition the electronic circuit forthe valve control is designed to receive a trigger signal for therelease of taste compound in pre-determined dosage. The signal could betriggered by monitoring a user's vital signal to assure that user isasleep prior to start releasing taste compound.

FIG. 7A illustrates another variation of a dispensing device 170 inwhich the device 170 simply comprises a stimulant tube 172 and a scenttube 174 each coupled to a reservoir or controller 176 that houses therespective stimulant and/or scent. Alternate variations contemplate theuse of an aromatic stimulant such that scent is triggered by the meredeployment of the stimulant. As shown in FIG. 7A, the tubes 172 and 174are merely affixed to the patient to intermittently deploy thestimulant. In an alternative variation, the tubes can be combined into asingle tube. Furthermore, the tubes can optionally be fitted with thesensors discussed herein.

FIG. 7B shows a Constant Positive Airway Pressure (CPAP) device 180combined with the teachings disclosed herein. As shown, the CPAP device180 can include a separate supply 182 to couple the CPAP device 180 to asource 184 of a stimulant 186. Alternatively, the CPAP device can beused with a self contained device as disclosed above.

The stimulant described above can take the form of a liquid of low orhigh viscosity, a solid, a semisolid or paste, a gas or a combinationthereof. The properties of the stimulus are such that delivery withinthe mouth causes a biological or natural reaction. This reaction caninclude generation of saliva to cause swallowing but in an amount thatdoes not awaken the user from a sleep state. Alternatively or incombination, the stimulant can cause movement of the tongue orrepositioning of the tongue in a forward position against the teeth.

FIG. 7C illustrates yet another variation of a dispensing device 170 inwhich the device 170 comprises a stimulant tube 172 coupled to asolution supply 173. A stimulant supply 186 can feed into the solutionsupply 173 along with a second substance 187. One variation contemplatesthe second substance 187 to dilute the effects of the stimulant to allowfor continuous dispensing of the solution over a period of time duringthe night or periodically.

The stimulant can comprise any number of tastes including, but notlimited to sweet, sour, bitter or salty.

Examples of liquid stimuli are solutions of Xylitol, saline and citrus.Smell stimuli include odors and fragrances that stimulate salivation andswallowing during sleep, such as banana, strawberry, orange, otherfruits, vanilla, or mint. Preferably the stimuli can be delivered to theuser over normal periods of sleep and as a long term therapy for snoringor sleep apnea, without causing untoward effects to the anatomy andphysiology, such as degradation of the teeth or gastric disturbances. Inthe cases of taste and smell stimuli, the stimulation applianceincorporates a reservoir that allows for delivery of the stimulus overthe sleep period.

Alternatively, in another embodiment, the compound that increasessalivation could be other fruit flavors or other food flavors of theparticular user's choice. The mouthpiece or retainer is either designedfor repeated use or disposable. Once the user wakes up in the morning,he/she will remove the device out of the mouth, rinse it and allow it todry. Next night prior to sleeping, the patient would insert a capsulecontaining taste compound in the device or reload the taste compoundreservoir, place it in the mouth and fall asleep. In the case of adisposable mouthpiece, optionally the capsule or reservoir could bepackaged preloaded with the taste compound or allow for placement of acapsule or filling of a reservoir, similarly to a reusable device. Inanother embodiment the reservoir comprises a primary reservoir, asecondary reservoir and a passive valve on the secondary reservoir thatopens at a prescribed pressure. The primary reservoir which contains thetaste compound fills the secondary reservoir at a uniform flow ratethrough an orifice between the reservoirs. The driving force for flowbetween the primary and secondary reservoir is enabled by gravity or,optionally, by a plunger driven by a spring. The secondary reservoirfills until it reaches a volume that exerts the cracking pressure of thepassive valve, allowing delivery of an aliquot of the taste compound.

Example 1

As discussed above, abnormal head and neck anatomy and decreasedpharyngeal dilator muscle tone are two primary contributors to OSA. Bothconditions affect the tongue and result in the tongue's having a centralrole in OSA. One variation of a device using a stimulant (e.g., aflavored substances) to engage the tongue and alleviate tongue-relatedobstruction can include the use of one or more pressure sensors withinthe existing intraoral device. For example, FIG. 2A illustrates sensors116 that will detect the presence or absence of the tongue in adesirable position within the mouth. FIG. 8A illustrates one example ofa fiberoptic pressure sensor (supplied by FISO Technologies Inc.,Quebec, QC, Canada).

In this example, the outer diameter of the sensor was 260±20 μm, and theouter diameter of the fiberoptic cable connecting to it (extending fromthe subject's mouth when deployed) was 1 mm. In some variations it isimportant that the sensors not interfere with tongue movement. Also, thepressure sensor (in this case the fiberoptic cable) should bewell-tolerated due to its small size. In the variation used, two sensors190 (FOP-M260 sensors) are placed within the intraoral device (as shownin FIG. 2A) on the lingual aspect of the dentition 116 to enable directtongue contact. The locations chosen are anteriorly in the midline andmore-laterally, between the canine adjacent to the first premolar.However, alternate placement of the sensor is well within the scope ofthis disclosure. In the present example, the sensors could be secured inposition with the use of medical-grade adhesive against the intraoraldevice, identically as for the stimulant supply tubing 108.

In cases where an optical sensor is used, the sensor relies onFabry-Perot whitelight interferometry to use a light source (brightincoherent light) that is split 50/50 within a 2×2 coupler. The lightpasses through the optical connector and optical fiber to reach thesensor, which is a Fabry-Perot interferometer (see FIG. 5). Within thesensor, the light is reflected, but a large number of parallel beamsescape the optical fiber core. These are redirected back into theoptical fiber core, creating a light interference pattern that isassociated with the distance between the semi-reflective mirrors in thesensor. Changes in pressure at the sensor tip alter the length of theFabry-Perot cavity in the sensor and thereby change the interferencepattern. The light from the sensor is reflected back through the opticalfiber to the coupler. The coupler then splits the light, with half ofthis light directed back to an optical box, where it is spread over aFizeau wedge that reconstructs the interference pattern and records itwith a charge-coupled device.

Use of the FISO Technologies FPI-HR system in combination with the oralimplant device described above allows for acquisition of pressures usingthe FOPM260 sensor at up to 15 kHz over a range of −300 to +300 mm Hgand accuracy within 2 mm Hg. Although two sensors were used and enable amore-thorough assessment of tongue neuromuscular activation than ispossible with one sensor. Any number of sensors is contemplated withinthe scope of this disclosure.

FIGS. 8B and 8C demonstrate the results of a custom fitted oralappliance (similar to that shown in FIG. 2A). In the experiment apatient received a 40% xylitol solution infused into the anterior oralcavity for 5 minutes at a constant rate of 0.1 ml/min. The infusion wasinitiated every 10 minutes, producing an alternating pattern of 5minutes on, 5 minutes off throughout the night. FIG. 8B presents theapnea-hypopnea index (AHI) results for individuals with mild to moderateOSA, while FIG. 8B presents the apneahypopnea index (AHI) results forindividuals with severe OSA. Overall, there was a decrease in theapnea-hypopnea index (AHI) from 37.5 to 17.1 events/hour, with thedecrease from 16.0 to 7.1 in mild to moderate OSA and 69.7 to 32.3 inthe severe OSA group. The changes in the mild to moderate OSA subgroup,including the decreases in AHI of >50% in all subjects and the lowlevels of residual AHI, have led to the eligibility criterion of mild tomoderate OSA in the proposed clinical trial. In addition to thereduction in AHI, there was a corresponding decrease in the arousalindex and no change in sleep architecture (normal percentage of time inREM sleep).

Example 2

1. Introduction:

The tongue plays an important role in snoring and obstructive sleepapnea, contributing to turbulent airflow and upper airway obstructionduring sleep. An intraoral device is used in this experimental exampleto deliver flavored substances in the anterior oral cavity, with thegoal of induced tongue chemoactivation and anterior tongue movementtowards the flavored substances. The effect of this chemoactivation isto open the airway by overcoming the natural decrease in muscle toneduring sleep that leads to posterior tongue prolapse. In this study,tongue sensors were incorporated into the intraoral device, placedimmediately posterior to the maxillary (upper) central dentition. Theobjective of this study was to examine tongue chemoactivation andanterior tongue movement associated with the administration of flavoredsubstances in the anterior oral cavity.

According to one aspect illustrated by this experimental study example,a tongue position sensor (“TSE”) assembly and method is configured todetect tongue repositioning activity to the sensor position. Moving thetongue anteriorly into such a position, in particular toward the frontteeth, repositions the tongue out of the posterior pharynx.

This TSE approach monitors the presence, and absence, of this protectivetongue repositioning activity against pharynx obstruction. The specificTSE embodiment constructed under this experimental example is notnecessarily configured for the additional directed purpose to alsomeasure all tongue positioning activities—and some of which are presentin the normal individual to prevent obstructive events. Pathology willgenerally occur via the tongue receding to the posterior pharynx andcausing obstruction. It is also considered highly beneficial to detectthe presence any one of multiple protective tongue activities, asindicating a likelihood that the tongue is non-obstructively positionedrelative to the posterior pharynx. In the setting of a therapy intendedto achieve this result, such detection also confirms the functionalsuccess of the therapy.

Devices and related methods that are configured to reposition the tongueout of the posterior pharynx have been proposed, and constructed,tested, and demonstrated that such tongue repositioning may resolve orat least improve these obstructive events and other related disorders.Certain such approaches are configured to stimulate tongue movement forsuch repositioning, i.e. as tongue repositioning stimulators (“TST”).Such a TST may be configured and operated by a number of mechanisms andmethodologies. Certain exemplary embodiments include, withoutlimitation: (1) the TST may be configured and operated to apply a forceto the tongue to directly move it into the desired anterior position; or(2) the TST may be configured and operated to apply a stimulation whichinvokes a biological response in the subject which moves the tongue intothe desired position; or (3) a combination of (1) and (2). Certainfurther embodiments of (2) above include, without limitation, astimulation media which is delivered via an appropriately configured TSTassembly and method in a manner to stimulate a response to cause thetongue positioning. This stimulation media may comprise, according tofurther embodiments, and without limitation: (a) a fluid, and which maytypically be a liquid, though may also be a gas; (b) a semisolid, paste,or gel; (c) a solid; (d) a flavor, taste, or smell invoking theresponsive tongue movement; or (e) a combination of any of thepreceding, i.e. a fluid flavor stimulus, such as for example a liquidflavor or taste stimulus—as is used in the present experimental studyexample.

Another aspect of the present disclosure provides a TST may beconfigured for passive delivery of the stimulus, such as for examplesimple passive dissolving of a stimulus material or diffusion of a fluidinto the mouth.

However, according to another aspect of this disclosure exemplified bythe present experimental study, a TST may comprise controlled deliveryof the stimulus, i.e. as a controlled TST or “cTST.” According to onebeneficial mode of this aspect, the cTST comprises a controller whichcontrols the stimulus delivery. In certain beneficial embodiments, thiscomprises controlled delivery of a stimulus media, which may be infurther embodiments, for example but without limitation, at least one ofa fluid and a flavor stimulus. A cTST comprising a controller to controldelivery of a fluid flavor stimulus is provided and used under thecurrent experimental study.

The controller of a cTST may control stimulus delivery according tovarious different desired delivery profiles, e.g. amounts, rates, or“dosage” regimen of the stimulus therapy over time. According to oneembodiment, this comprises a relatively fixed profile for constantdelivery or dosing regimen of the stimulus therapy over time (such asfor example during sleep). However, according to another embodiment,this comprises controlling the delivery profile and dosing regimen tochange over time, e.g. between different conditions (i.e. amount and/orrate of stimulus delivery). Such changing profile may comprise, forexample, a continuous rate of change, or discontinuous rate of change,or a combination thereof in different time intervals, over a therapydosage period (e.g. during sleep). This change can be between on and offconditions—either in absolute terms, or in functional context withrespect to being above or below, respectively, a threshold for achievingthe intended results of stimulation. It is thus appreciated that thiscontrolled delivery may be modulated to change between levels of appliedstimulus (which may be according to a pattern, such as a cycle; or maybe another form of changing profile).

The controller of a cTST system and method may comprise a relativelysimple control mechanism, or may be more complex. According to oneexample, it may comprise a pump for delivering a fluid stimulusaccording to either fixed or adjustable delivery rates, change(s) inrate, and/or other settings which may be either manual or automated, ora combination thereof. The controller may also comprise a computersoftware program embedded in a non-transitory computer readable mediumand configured to be run by a processor, and/or a processor configuredto run and process an embedded computer software program in anon-transitory computer readable medium.

The current experimental example involves a particularly beneficial cTSTembodiment which comprises a controller, liquid stimulus source, andoral delivery assembly—all assembled in an overall system for controlledpump delivery of the liquid flavor stimulus at an anterior locationwithin the mouth, in particular behind the front teeth. The flavorstimulus applied in the proper position, in particular posteriorlyadjacent to the front teeth, stimulates movement of the tongue forwardinto the proper anatomical position and out of the posterior pharynx(i.e. protective tongue repositioning activity). In addition to thistype of protective repositioning, there may also be additionalprotective responsive mechanisms, such as that muscle tone is improvedsufficient to remove the tongue out of the posterior pharynx such thatit is no longer obstructing breathing.

According to another aspect exemplified by the embodiment of thisexperimental example, a TST is provided in combination with a tongueposition sensor (or “TST-TSE”) system. According to one mode of thisaspect, the TSE is used to assess the performance of the TST tostimulate the tongue into the anterior protective repositioningactivity. According to another mode, a cTST is combined with the TSE toform a “cTST-TSE” combination system. Further to this mode, the sensedtongue position information provided by the TSE is used as a real-timediagnostic basis and input into the cTST, and at least in part by whichthe configuration and operation of the controller of the cTST is based.In one embodiment, in response to the TSE sensing an absence of (orreduction or movement away from) the anterior protective position, thecTST is configured and operated to control the stimulus delivery toapply the stimulus in a manner that causes the tongue to move into theanterior protective position. In another embodiment, in response to theTSE sensing the tongue is in the anterior protective position, the cTSTis configured and operated to control the stimulus delivery to stop orreduce the application of the stimulus. This may provide a benefit, forexample, to prevent overstimulation and potential wakening of thesubject, or prevent habituation or desensitization of the tonguemovement response to the applied stimulus.

2. Purpose:

The current study was designed and conducted as a 14 day trial of asingle control subject without a history of obstructive sleep apnea. Thetest subject was subjected to consecutive nightly exposure to a liquidstimulus, xylitol, administered in the anterior chamber of the mouth (oranterior oral cavity). This was conducted via a new and useful cTSTdelivery assembly and method constructed for stimulant delivery via anoral appliance according to a particularly beneficial embodiment of thisdisclosure. A TSE was also included, also incorporating the oralappliance, in an overall cTST-TSE system. The hypothesis entering theexperiment was that the TSE will be able to demonstrate the anteriorprotective tongue repositioning activity in response to this appliedxylitol exposure via the cTST, thus showing that in response to thenovel cTST therapy:

(a) the subject's tongue moves forward into the anterior protectiveposition, and will trigger the sensor of the TSE; and

(b) the anterior protective tongue repositioning activity is repeatablenight after night and does not habituate or disappear over the two weekperiod.

During the 14 night trial, certain parameters were varied to compareeffects, via changes in pressure at the sensor of the TSE, of variousrates and intervals of xylitol exposure via the cTST, includingexamining for differences in acute responses for multiple infusion ratesand dosing intervals as well as for habituation over the 14 day period.

3. Materials:

A custom cTST-TSE mouthpiece or dental retainer, stimulus deliverycontroller, liquid flavor stimulus, and pressure sensor (includingrecording means) were all prepared and assembled in an overall cTST-TSEsystem, illustrated in partial schematic view in FIG. 9, as follows:

a. Custom TST-TSE Dental Retainer

A custom mouthpiece was configured as a dental tray made bythermoforming a plastic retainer to a mold of the patient's teeth. Thecustom configuration constructed and used is palatal arch-less, andsecured by form fitting to the teeth. This shares certain similaritiesto such dental retainer trays made and sold under the name “Invisalign™”or otherwise for braces or certain teeth whitening trays. However, thecurrent dental tray retainer also comprises certain distinct differenceswhich are both structurally and functionally unique—and exemplifyvarious inventive aspects of the present disclosure concordant with theunique functional purposes intended.

The dental retainer is vacuum formed with an Essix™ Vacuum

Thermoforming Machine, model #85000 sold by “Dentslpy™.” While variousmaterials may be suitable and used for this purpose, the material chosenfor this particular experiment is plastic, and more specifically aDentsply™ plastic: “PET Essix A+.” The plastic tray was constructed forthis particular experiment with a wall thickness of about 0.02 inches.

As two particularly unique features of the present embodiments of thisexample, two tubes were also secured to the tray, in particular by UVbonding each of two IV tubes to the tray for purpose of this specificexperiment (though other bonding, securement, or integration of thefeatures may be sufficient). These tubes were secured in a configurationto create two ports, respectively, on the posterior lingual side of theanterior two front teeth—and which were generally adjacent or “side byside” (though exact side by side adjacency is not considered absolutelynecessary, and other relative locations may be suitable). The tubes werealso configured to extend anteriorly away from the tray, teeth, andmouth and externally of the patient. This construction provides theunique custom result of a delivery tube and respective delivery port forstimulus delivery to the posterior lingual side of the anterior teeth,and sensor tube and respective sensor port at a similar, generallyadjacent, location. In the physical embodiment constructed for thisexperiment, these tubes terminated in luer lock ports. One port wasconnected to an infusion pump, with a 30 BD syringe filled with the 40%xylitol solution.

b. Liquid Flavor Stimulus

Xylitol sugar (sweetener frequently used, such as for example inTrident™ gum) was mixed with tap water in 40% concentration to providethe liquid flavor stimulus. This was retained and dispensed during theexperiment using a standard, commercially available 30 ml “BD” Syringe.Delivery was accomplished via the standard small bore IV tubing notedabove as secured to the TST-TSE dental retainer.

c. Stimulus Delivery Controller

An infusion pump (Baxter™ AS40™ Auto Syringe Infusion Pump™) was alsoprovided to control the delivery via the syringe, via delivery profileparameters that were configured to a variety of settings for purpose ofthe test agenda and hypotheses.

d. Pressure Sensor

Pressures were collected using a commercially available FOP-F125™pressure sensor. This sensor was located adjacent to the inlet port forinfusion of the xylitol solution, directly behind the maxillary (upper)central dentition. The sensor tip was positioned within anauto-inflating, cotton fiber-filled polyurethane bubble that wasdesigned as part of a closed system with the sensor. The pressure sensorwas also coupled to the pressure tubing secured to the TST-TSE dentalretainer. The sensor was also connected to a signal processor and thesignal processor was connected to a PC with analytic software. Morespecifically, it was connected to a FPI-HR Module™ signal conditioner(manufactured by FISO™ Inc.). Data collected was then recorded to astandard PC, using Evolution™ software also provided by FISO™ Inc.

4. Methods

The test subject was fitted with the custom TST-TSE retainer. Oneproximal port was connected to the infusion pump, per the 30 BD Syringefilled with 40% Xylitol solution. Xylitol infusion rate was set atvarious parameters, as described in further detail below.

A second proximal port was connected to IV pressure tubing, leading to asealed chamber containing the sensor. The sensor was connected to asignal processor and the signal processor was connected to a PC withanalytic software, as described above.

FIG. 9 shows an embodiment of the cTST-TSE system 200 described above,with certain components shown schematically for simplicity. Morespecifically, FIG. 9 shows (though not readily visible as it is clear) acTST-TSE retainer 202 on a white model of teeth 201, with tubes 204, 206extending from the cTST-TSE retainer 202 and terminating in couplerssuch as shown at luer lock 208 for tube 206. These tubes are fluidlycoupled via passageways formed in the retainer 202 to a dispensing portand sensor, respectively, at adjacent delivery and sensor locations,respectively, on the central anterior aspect of the oral cavityposteriorly adjacent to the middle two front incisor teeth (not revealedin the detail shown). Tube 204 comprises a delivery tube and is alsofluidly coupled to a controlled stimulus delivery assembly 210 locatedexternally of the mouth and comprising a source of stimulant 212 and acontroller 214. Tube 206 comprises a sensor tube and is also fluidlycoupled to a pressure sensor processing assembly 216 via luer lockcoupler 208.

Stimulant from the source 212 is delivered via delivery tube 204 to thedispensing port at the delivery location. In response, the tongue isstimulated to be repositioned to an anterior protective position againstthe front teeth and thus with applied pressure against the sensor at thesensor location. This is conveyed via sensor tube 206 to the sensorprocessor 218. In a cTST system, the sensed pressure is converted to asignal with a value that is communicated to the controller 214 in afeedback coupling 216, e.g., electrical communication between the twoappliances. While it is considered a beneficial embodiment (though notnecessary) of the present disclosure to control the stimulus deliveryvia the sensed tongue position, this coupled feedback loop between wasnot incorporated into the current experimental study design. In thecurrent experimental design, the sensed pressure is processed into datawhich is recorded for analysis, as shown at block 220 schematically inFIG. 9. Screen shots and data files were collected for comparativeanalysis. Controlled stimulant delivery was instead managed bypre-determined parameter inputs to the controller under a controlledexperimental design with controlled ranges of delivery variables.

5. Results

Results follow in 4 basic categories: (i) Examples of “on” and “off”states of TST xylitol delivery; (ii) changing delivery rates, per pilotstudy protocol, 5 min on (about 100 μL/min), 5 min off (about 0 μL/min);(iii) changing delivery, at shorter Intervals of (a) 2 min on, 3 minoff, with “on” at various rates of 100, 50, and 25 μL/min, and (b) 3 minon (about 33 μL/min), 3 min off; and (iv) continuous “on” state (about150 and 33 μL/min).

(i) Examples of Device ON/OFF States

FIG. 10 shows a graph of results according to sensed anterior tonguepressure vs. time (example, ON/OFF states). Certain relevantobservations include, without limitation, the following:

(a) from 0-1,000 seconds, subject is awake with several events ofanterior protective tongue repositioning activity apparent via sensedpressure data recorded;

(b) from 1,000 to 3,650 seconds, the device is in place but OFF. Therecorded pressures during this period reveal no apparent anteriorprotective tongue repositioning against the sensor during the OFF mode;and

(c) starting at 3,750 seconds, the controlled pump device assembly isset to continuous on. Recorded pressure results show an appreciableamount of anterior protective tongue repositioning activity during thisperiod.

FIG. 11 also shows a graph of results according to sensed anteriortongue pressure vs. time (example, OFF only). The device is in place andworn by the subject, but set to OFF. The results demonstrate there isalmost no anterior protective tongue repositioning activity when thecontrolled stimulus delivery device is turned off:

(a) limited activity at 100 seconds, reflecting awake state, then againat around 2,000 seconds (a possible swallowing event); and

(b) the recorded pressure data over the rest of the recording periodreveals virtually no anterior protective tongue repositioning activity,though the tongue is not believed to have been obstructive to thepharynx (perhaps due to good tone or other protective position), asevidenced by lack of suspected obstructive events or related sleepdisorder.

(ii) Per Pilot Study Protocol, 10 min ON/OFF Cycles (5 min ON, 5 minOFF, rate=100 μL/min)

FIG. 12 shows a graph of frequency of sensed anterior protective tonguepositioning events (per second) vs. time (consecutive nights over 14 dayperiod), according to this test protocol. More specifically, FIG. 12shows graphical results using the same rates and intervals on fourseparate nights throughout the 14 day trial demonstrating that thetongue activity is generally repeatable (obviously within a certainrange of variability) night after night and does not reveal a trend thatthere is habituation to the stimulus or disappearance of the biologicrepositioning response over the two week test period.

FIG. 13 shows a graph of same results featured in FIG. 12, per frequencyof sensed anterior tongue positioning events (per second) vs. time(consecutive nights over the 14 day period, in split-night view).However, FIG. 13 shows a closer look at the same nights in same testsubject, comparing the first half of the night to the second half (i.e.“split night” view or analysis). While again certain range ofvariability is shown, out to night 14 similar activity is observed aswas observed at night 4, and without significantly apparent differencebetween first and second halves of the night on that 14^(th) nightfollowing continual treatment over the 2 week period.

(iii) Shorter Interval, 5 or 6 min ON/OFF Cycles (2 or 3 min ON, 3 minOFF, at Various Rates)

FIG. 14 shows a bar graph of results according to frequency of sensedanterior protective tongue repositioning events (per second) vs. time(consecutive nights over 14 day period). More specifically, the FIG. 14bar graph shows results of using a shorter interval than the pilot trialprotocol with various rates. As shown over this test period, the sensedfrequency of anterior protective tongue repositioning activity appearsto reduce in direct relationship with reducing stimulant delivery rateacross the matrix from 100 uL/min on night 5 to 25 uL/min by night 13.This again suggests confirmation that the stimulant delivery appears tobe playing an active role in the desired tongue repositioning activity.

FIG. 15 also shows a bar graph of results per frequency of sensedanterior protective tongue repositioning activity events (per second)vs. time (consecutive nights over 14 day period). However, while FIG. 15provides a closer look at the same nights in same subject as FIG. 14,this graph of FIG. 15 compares the first half of the night to the secondhalf (when available) in split night analysis.

(iv) Continuous Rate (Continuously on, at Two Different StimulantDelivery Rates)

FIG. 16 also shows a bar graph of frequency of sensed anteriorprotective tongue repositioning activity events (per second) vs. time(consecutive nights over 14 day period). However, this is a graph ofresults during continuous flow, with no pauses in delivery of xylitol,but comparing two different stimulant delivery rates. An obviousreduction is apparent in sensed events in direct relationship to thereduction from the 150 uL/min rate on night 1 (about 9.5 events), andthe 33 uL/min rate on night 12 (<4 events)—in fact the >50% reduction indelivery rate resulted in >50% reduction in the desired tonguerepositioning events.

6. Additional Analysis/Discussion

FIG. 17 shows a graph of sensed tongue movement to the protectiveanterior position as a function of varying stimulant delivery rates. Theresults show that tongue movement is maintained at even lower rates. Itis noted that with no flavor there appears to be a considerable drop-offin response. It is also noted in this data that certain points reflectcontinuous on, whereas others represent cycled on/off conditions (asreflected in the legend).

FIG. 18 also shows 14 days of consecutive treatment at various rates andprotocols.

The current Example 2 reflects data from a 14 day trial of a singlecontrol subject, without a history of obstructive sleep apnea. Aconsecutive nightly exposure to xylitol was administered in the anteriororal cavity via the novel cTST-TSE system described.

The experimental data demonstrates that the tongue moves forward and isdrawn to the anterior oral cavity against the front teeth with the novelanterior protective tongue repositioning stimulation treatment used. Theaffect is not appreciably present with the device in place and turnedoff. The presence of the oral appliance alone, not turned on, is notsufficient to cause the movement of the tongue. Additionally, the studyalso reveals that this cannot be optimally achieved just by using plainwater without a flavor, since the presence of flavor appears to greatlyenhance the tongue movement—as reflected in this data. This clearlydemonstrates the mechanism of action, where the tongue is stimulated tocome forward in the presence of flavor stimulus when administeredaccording to the unique systems and methods used in this experiment.This is expected to provide protective benefit during sleep, since it isknown that bringing the tongue forward from a posterior position to theanterior oral cavity as in this experiment clears the posterior pharynxand reduces symptoms of obstructive sleep apnea.

In addition, there was no appreciable habituation observed after twoweeks of this unique therapy. There were different rates used over the14 day study, but comparing the four nights of standard rates “protocol”of treatment (i.e. on for 5 min then off for 5 min) no relevant decreasein tongue activity is observed. In fact, the second two nights of thistreatment resulted in a greater frequency of tongue movement than thefirst two protocol nights. This suggests support for a hypothesis thatthere is actually a conditioning response that takes place, and thatsuccessive treatments grow stronger in their stimulation impact andresults.

The observations in this study also reveal that the variability ofresponse using different rates and hourly volumes appears to be withinthe night to night variability of identical treatments. This suggeststhat the frequency of tongue movement is not likely to be solelydependent on the volume of delivery. Volumes can be reduced such thatthe frequency of stimulation, the anterior movement of the tongue isconsistent.

As would be readily appreciated by one of ordinary skill, while certainspecific values and other numbers are recited herein this disclosure,and are considered to provide particularly beneficial examples, unlessotherwise stated such values are not intended to necessary limit thebroader aspects of the disclosure which they exemplify. Unless statedotherwise, such exemplary values are not necessarily considered exact orabsolute—and the exemplary values should be considered in “about” terms.Slight variances may be made to specifically stated values or rangeswithout departing from the broad aspects exemplified. For example, mostdimensions or performance measures, whether stated in the singular,ratio, or range for example, will typically be subject to certaintolerances of the materials, structural designs, operating environment,and methods embodied in the featured numbers. Moreover, variations mayalso be deliberately made from such specific values disclosed, but whilestill accomplishing similar or equivalent objectives and results, andstill falling within the broader aspects of the disclosure. For example,while remaining subject to and without limiting the preceding aspects ofthis paragraph above, a tolerance of plus or minus about 10 to about 20percent of such specified values will typically still be consideredequivalent and falling within the intended scope of the specific valuesherein described.

As would also be apparent to one of ordinary skill, such “values” notedimmediately above relate to quantitative or “numeric” values, and alsoqualitative values. For example, certain exemplary embodiments describedhereunder recite an “intermittent” stimulus delivery, and which incertain further embodiments is described to be between “on” and “off”conditions or states of stimulus delivery. It is readily appreciated byone of ordinary skill that such conditions or states should beconsidered contextual to the related purpose and intended functionalresults of the respective states. For example, an “on” condition orstate of stimulus delivery may be achieved when the stimulus isdelivered at or above a certain threshold intended to achieve afunctional stimulated result; whereas conversely and “off” condition orstate of stimulus delivery may be achieved by a stimulus deliveryprofile or dosage regimen below that threshold—i.e. functionallyequivalent, contextual to the intended result of stimulation, to acomplete cessation of any stimulus delivery. Moreover, while an“intermittent” change may be accomplished in discrete intervals that maynot be continuous, a continuous change in stimulus delivery amount orrate may be equivalent to an interval change when the change is betweensuch “on” and “off” conditions relative to being above or below astimulus threshold, respectively.

The present detailed embodiments have been variously described byreference to delivering stimulants or stimulus, and in more particularapplications specifically for delivering stimulants to the mouth forstimulating a tongue, and in further detail for stimulating tonguerepositioning, and still more specifically to Type 1 or anteriorposition within the mouth. However, other therapies may also bedelivered according to these systems and methods and still fall withinthe broad intended scope of the various aspects contemplated hereunder.

For example, various different therapeutic agents may be deliveredaccording to the systems and methods herein described. Such agents maybe for example materials or molecular agents, which may be in variousdifferent preparations for delivery, such as fluid (e.g. liquid or gas),solid, semi-solid, gel, paste, suspension, powder, etc. Or, thetherapeutic agent may be in another form such as an electrical current(e.g. RF current for example), thermo-energy (e.g. either heating orcryo/cooling), optical energy (which may provoke an optical response intissue or provide another form of thermal heating), etc. For one moredetailed example for purpose of further illustration and understanding,a low current/voltage RF signal may be delivered similarly in context ofthe oral delivery systems and methods as described herein with respectto delivering a fluid flavor stimulant (e.g. according to the“Examples”). This may be either in the alternative or addition to suchfluid stimulant delivery. For example, delivering such electricalcurrent to a similarly positioned anterior location in the mouth, suchas described above for delivery port of the xylitol delivery of Example2 (e.g. lingual side of front incisor teeth), may also stimulate atongue repositioning response into the anterior position of the mouth asdesired. In another more detailed illustrative example, such current maybe delivered via a current source either coupled directly to the oraldevice or from outside the mouth via a delivery assembly (e.g.electrically via electrical leads similar to fluid coupling via deliverytubes described above). In a further example, this current may also beexposed at an electrode which is located at similar position as thefluid delivery port of the Example 2. In such example, the electrode maybe bi-polar with the two electrodes on the oral device itself, or may bemonopolar and work via a ground patch placed elsewhere on the patient(as in other RF current medical device assemblies previously disclosed).

Also in the alternative or combination with one or more of the aboveexamples, a thermal heating or cooling element may also be provided atsuch a location on the oral device in similar anterior position withinthe mouth—and which may also provide such tongue stimulus forrepositioning.

Other variations or modifications to the detailed embodiments above canalso be made, and remain within the broad aspects intended to becaptured by this disclosure. For example, many different specificsensors and related structural arrangements, for sensing variousdifferent parameters, can be incorporated into the sensor embodimentsherein shown and described, as well as other embodiments as would beapparent to one of ordinary skill based upon a review of thisdisclosure.

For further example, optical sensors may be employed, with variousalternative assemblies coupling them to mouthpieces. According to onesuch example for illustration, a light source is coupled to anillumination port on the oral device and configured to transmit anillumination light signal from the illumination port into the mouth. Thesensor according to this arrangement may comprise an optical sensorcoupled to the oral device at the sensor location. Further to thisarrangement, the sensor location is positioned relative to theillumination port such that the optical sensor is configured to sense areflected light signal that is reflected in the mouth from theillumination light signal transmitted into the mouth from theillumination port.

According to an additional embodiment, an optical fiber is provided witha first end portion with a first end optically coupled to the oraldevice at the sensor location and also to the mouth in the implantconfiguration, and a second end portion coupled to the optical sensorlocated outside the mouth when the oral device is in the implantconfiguration. Further to this example, the reflected light signal isoptically coupled from the sensor location in the mouth to the opticalsensor outside of the mouth via the optical fiber.

In another particular example for further illustration, an optical fiberis provided with a first end portion with a first end optically coupledto the oral device at the illumination port and also to the mouth in theimplant configuration, and a second end portion coupled to the lightsource located outside the mouth when the oral device is in the implantconfiguration. Further to this example, the illumination light signal isoptically coupled from the light source outside of the mouth to theillumination port and into the mouth via the optical fiber.

According to another example, an optical fiber couples the illuminationport on the oral device in the mouth, at a first end of a first endportion of the optical fiber, to the light source located outside themouth, at a second end of a second end portion of the optical fiber;whereas an optical fiber also similarly couples the sensor location onthe oral device in the mouth to an optical sensor outside of the mouth.

Still further variations are contemplated according to this example. Inone such further variation, the illumination port and the sensorlocation are coupled to the oral device at first and second separate butadjacent locations; and the first and second end portions of each of thefiber optic delivery members are separate, distinct fiber optic deliverymembers. Further to this variation, the first end portions of each ofthe first and second fiber optic delivery members may also be, at leastin part, bundled adjacently together. According to another variation,the first end portions of each of the first and second fiber opticdelivery members comprise the same common fiber optic delivery member.According to another variation, the second end portions of each of thefirst and second fiber optic delivery members comprise the same commonfiber optic delivery member; and the light source and optical sensor areeach coupled to the common second end (typically with a splitter,separator, or other mechanism known in the art for measuring transmittedand reflected light via a common fiber optic. In still another furthervariation, where a common optical fiber is used at the first endcoupling to the device for transmitting and receiving reflected light atthe optical interface in the body, the second end portion is bifurcatedto comprise first and second optical couplers. The first optical coupleris configured to be coupled to the light source, and the second opticalcoupler is configured to be coupled to the light sensor. Further to thisvariation, light transmitted from the light source via the first opticalcoupler and light received by the light sensor via the second opticalcoupler are transmitted via the common first end portion of the opticaldelivery member.

Furthermore, other therapies may be also be provided for delivery anduse according to the structural system and method aspects, and theexemplary embodiments of this disclosure. This also may be either inaddition to or in the alternative to the specific therapies also hereindescribed. For example, this may include therapies other than tonguestimulation or repositioning, other stimulant delivery and stimulustherapies related thereto, or other therapies than stimulation ordelivering, or other therapies than those which may be related to thetongue. For example, other therapeutic agents may be employed for othermedical or dental purposes, such as for example pharmaceutical agents(e.g. drugs), as the present disclosure provides for a beneficial newapproach for oral drug delivery. Accordingly, a wide range ofapplications may be satisfied for many different target objectivessuitable for such oral agent delivery and consumption. This may includesomething as simple as delivering antiseptic, anti-bacterial, or otherform of mouth cleansing, hygienic, or breathening agent, or assignificant as delivering a drug (either over the counter,nutraceutical, or prescription) that has either oral, lingual, or otherbiologic activity for various medical purposes through absorption orconsumption via the oral delivery. According to one such example, forillustration and not to limit the broad scope of the foregoing, fluidagents may be delivered orally via these systems and methods and whichmay treat certain nasal or sinus ailments or conditions.

The devices, systems and methods as described herein can thus be appliedfor the treatment of various diseases and conditions other than snoringand/or OSA. For example, the disclosed appliance and delivery methodscan be used to deliver suitable agents for the treatment of oral hygieneand xerostomia, as well as any other treatment that can benefit fromhaving a stimulant applied in the manner disclosed herein.

Certain embodiments disclosed relate to delivering therapeutic agents,such as stimulants, into the mouth via an oral device. Such embodimentscontemplate a broad scope with respect to the particular preparation forsuch agents in terms of the specific type of material (e.g. fluids,solids, etc.), as described elsewhere herein. These alternatives includein certain regards gas preparations for therapy delivery. However, it isalso appreciated that gasses are characterized with properties thatrapidly fill a volume or space in which they are introduced. In moredetailed embodiments where isolated local delivery to a particular partof the mouth is desired, e.g. only the anterior portion at or adjacentthe front incisor teeth, gas may be a non-ideal preparation to optimallyachieve the intended result. For example, where anterior tonguerepositioning is desired toward the front teeth, delivery of gas at thatanterior location may instead rapidly migrate toward the posterior mouthand/or throat, and thus mitigate the local target of the stimulus fromits intended anterior location. Accordingly, it is appreciated incertain such embodiments that a “non-gas” category of materialpreparation of the agent (e.g. tongue repositioning stimulus) isconsidered particularly beneficial (vs. a gas alternative).

From the description herein, it will be appreciated that methods,devices, and systems are disclosed for controlled delivery of a therapy,such as a stimulant, to a mouth of a subject via an oral devicepositioned in a secured configuration in the mouth. At least one of atongue position stimulator (TST) and tongue position sensor (TSE) isprovided, according to certain aspects. According to another aspect, astimulus is delivered to the mouth and/or tongue via a mouthpiecesecured to the subject's teeth. In another regard, a stimulus isdelivered that generates a natural response to eliminate or reduce sleepdisorders, such as for example at least one of snoring and obstructivesleep apnea. In certain embodiments, the therapy delivery comprises atleast one of: isolated delivery to only an anterior portion of the mouthat or adjacent to the front incisors, a non-gas preparation oftherapeutic agent, and either via coupling an external reservoir to theoral device or coating the therapeutic agent or stimulant onto adispensing surface of the oral device.

In addition to the disclosure herein, various aspects, modes,embodiments, features, and variations disclosed hereunder are summarizedas follows.

1. One embodiment is a method for treating sleep disorder breathing in asleeping individual, comprising: providing a stimulant that induces atleast one natural response within a mouth of the sleeping individualwhen the stimulant enters the mouth; delivering the stimulant at alocation behind one or more teeth in the mouth to induce at least onenatural response to reduce sleep disorder breathing and improve theability of the sleeping individual to maintain a sleep state; andchanging delivery of the stimulant.

According to another embodiment, the changing of the delivery comprisesreducing the delivery. In another embodiment, the changing comprisesintermittent changing. In another embodiment, the delivery reductioncomprises intermittently reducing delivery.

2. Another embodiment is the method of embodiment 1, wherein theintermittent reduction comprises intermittently pausing the delivery ofthe stimulant.

3. Another embodiment is the method of embodiment 1, wherein theintermittently reduced delivery temporarily ceases inducing the at leastone natural response.

4. Another embodiment is the method of embodiment 1, wherein theintermittently reduced delivery prevents the stimulant from waking theindividual.

5. Another embodiment is the method of embodiment 1, wherein providingthe stimulant comprises automatically delivering the stimulant from asupply source while the individual is in a sleep state.

6. Another embodiment is the method of embodiment 1, wherein the naturalresponse comprises an activity comprising at least one of salivation,forward movement of the tongue, repositioning of the tongue, swallowingand a combination thereof.

7. Another embodiment is the method of embodiment 6, wherein at leastone of the activities reduces vibrations of a soft palate or uvulawithout waking the individual.

8. Another embodiment is the method of embodiment 1, wherein providingthe stimulant includes positioning an oral appliance within the mouthhaving a delivery port that delivers the stimulant to the tongue.

9. Another embodiment is the method of embodiment 8, where positioningthe oral appliance within the mouth comprises positioning the oralappliance on at least one of the lower front teeth such that thedelivery port of the oral appliance is directly adjacent to theposterior side of the lower front teeth.

10. Another embodiment is the method of embodiment 8, where positioningthe oral appliance within the mouth comprises positioning the oralappliance on at least one of the upper front teeth such that thedelivery port of the oral appliance is directly adjacent to theposterior side of the upper front teeth.

11. Another embodiment is the method of embodiment 8, where the oralappliance comprises at least one of a mandibular advancement device, acontinuous positive airway pressure device, a mouthguard, a custommolded mouthpiece, and a retainer.

12. Another embodiment is the method of embodiment 8, where the oralappliance comprises an internal reservoir fluidly coupled to thedelivery port, the internal reservoir containing at least a portion ofthe stimulant, and where the delivery port comprises a valve, whereproviding the stimulant comprises opening of the valve to dispense thestimulant.

13. Another embodiment is the method of embodiment 1, where providingthe stimulant comprises providing an external reservoir containing thestimulant.

14. Another embodiment is the method of embodiment 1, further comprisingproviding a second stimulant to trigger an olfactory response in thesleeping individual.

15. Another embodiment is the method of embodiment 1, where thestimulant comprises a substance comprising a taste selected from a groupconsisting of a sour taste, a citric taste, a sweet taste.

16. Another embodiment is the method of embodiment 1, where thestimulant comprises a taste selected from a group consisting of xylitol.

17. Another embodiment is the method of embodiment 1, whereintermittently reducing delivery of the stimulant comprises reducing thestimulant delivery until a triggering signal returns an increaseddelivery of the stimulant.

18. Another embodiment is the method of embodiment 17, furthercomprising: a dispensing unit cooperating with a sensor; wherein thetriggering signal is generated in response to the sensor; and whereinthe dispensing unit is triggered to increase delivery of the stimulantin response to the triggering signal.

19. Another embodiment is the method of embodiment 17, wherein thedispensing unit is in electrical communication with the sensor.

20. Another embodiment is the method of embodiment 18, wherein thesensor comprises a sensor selected from the group consisting of apressure sensor, an optical sensor, a sound sensor, a movement sensor,an electro-magnetic sensor.

21. Another embodiment is the method of embodiment 18, where the sensoris positioned in the mouth and generates a signal based on a movement orposition of the tongue.

22. Another embodiment is the method of embodiment 18, where the amountof stimulant delivered is determined by the triggering signal.

23. Another embodiment is the method of embodiment 17, furthercomprising measuring a degree of tongue movement with the sensor andusing the triggering signal to determine the amount of stimulant basedon the degree of movement.

24. Another embodiment is the method of embodiment 1, where deliveringthe stimulant and intermittently reducing delivery of the stimulant aretimed with an event comprising respiration, respiratory effect,respiratory flow, hypoxia, hypopnea, oxygen saturation, or pausing thestimulant until a triggering signal restarts delivery of the stimulant.

25. Another embodiment is a method for minimizing sleep disturbances inan individual, the method comprising: positioning a dispensing unitwithin a mouth of the individual, where the dispensing unit comprises atleast one port adjacent to a tongue; providing a supply of a stimulantthrough the port that induces a biological response in the mouth of theindividual; controlling delivery of the stimulant between a firstdelivery phase, in which the stimulant is delivered to the mouth toinduce the biological response and a second delivery phase, during whichdelivery of the stimulant to the mouth is reduced form the firstdelivery phase.

26. Another embodiment is the method of embodiment 25, wherein thesecond delivery profile comprises substantially stopping delivery of thestimulant.

27. Another embodiment is the method of embodiment 25, whereincontrolling delivery of the stimulant permits periodically inducing thebiological response without waking the individual.

28. Another embodiment is the method of embodiment 25, wherein providingthe supply of the stimulant comprises automatically dispensing thestimulant while the individual is in a sleep state.

29. Another embodiment is the method of embodiment 25, where providingthe supply of the stimulant comprises metering the stimulant to inducethe biological response without waking the patient.

30. Another embodiment is the method of embodiment 25, furthercomprising: containing at least a portion of the stimulant within aninternal reservoir of the dispensing unit that is fluidly coupled withthe port; and wherein providing the supply of the stimulant comprisesdispensing the stimulant from the internal reservoir through the port.

31. Another embodiment is the method of embodiment 30, wherein providingthe supply of the stimulant comprises opening a valve to dispense thestimulant from the internal reservoir through the port.

32. Another embodiment is the method of embodiment 30, wherein thesupply of the stimulant is fully contained within the reservoir suchthat the dispensing unit is fully contained within the mouth.

33. Another embodiment is the method of embodiment 30, furthercomprising providing a remainder of the stimulant in an externalreservoir that is fluidly coupled to the internal reservoir.

34. Another embodiment is the method of embodiment 25, furthercomprising: containing at least a portion of the stimulant within anexternal reservoir located outside of the dispensing device and mouthand that is fluidly coupled to the port; and delivering the stimulantcomprises dispensing of the stimulant from the external reservoirthrough the port into the mouth.

35. Another embodiment is the method of embodiment 25, wherein thebiological response comprises salivation, forward movement of thetongue, repositioning of the tongue, swallowing, or a combinationthereof.

36. Another embodiment is the method of embodiment 25, whereinpositioning the dispensing unit within the mouth comprises positioningthe dispensing unit on at least one of the lower front teeth such thatthe delivery port of the dispensing unit is directly adjacent to theposterior side of the lower front teeth.

37. Another embodiment is the method of embodiment 25, wherein thedispensing unit comprises a mandibular advancement device, a continuouspositive airway pressure device, a mouthguard, custom molded mouthpiece,or a retainer.

38. Another embodiment is the method of embodiment 25, furthercomprising providing a second stimulant to trigger an olfactory responsein the sleeping individual.

39. Another embodiment is the method of embodiment 25, wherein thestimulant comprises a substance comprising a taste comprising at leastone of a sour taste, a citric taste, and a sweet taste.

40. Another embodiment is the method of embodiment 25, wherein thestimulant comprises xylitol.

41. Another embodiment is the method of embodiment 25, furthercomprising providing a triggering signal to control delivery of thestimulant between the first delivery phase and the second deliveryphase.

42. Another embodiment is the method of embodiment 41, furthercomprising: a sensor coupled to the dispensing unit; and wherein thetriggering signal is generated in response to a parameter sensed by thesensor.

43. Another embodiment is the method of embodiment 42, wherein thedispensing unit comprises the sensor.

44. Another embodiment is the method of embodiment 42, where the sensorcomprises a pressure sensor, an optical sensor, a sound sensor, amovement sensor, an EEG sensor, an EMG sensor, or an electro-magneticsensor.

45. Another embodiment is the method of embodiment 42, furthercomprising positioning the sensor in the mouth and generating a signalbased on a movement or position of the tongue or a movement or positionof the jaw.

46. Another embodiment is the method of embodiment 42, where the amountof stimulant delivered is determined by the triggering signal.

47. Another embodiment is the method of embodiment 42, furthercomprising: measuring a degree of tongue movement with the sensor; andusing the triggering signal to determine the amount of stimulant basedon the degree of movement.

48. Another embodiment is the method of embodiment 42, furthercomprising: measuring a degree of jaw movement with the sensor; andusing the triggering signal to determine the amount of stimulant basedon the degree of movement.

49. Another embodiment is an oral device for dispensing a stimulant thatproduces a biological response within the mouth to reduce sleep disorderbreathing in an individual, comprising: a device body having a dentalcavity for removably nesting with one or more structures within themouth; a dispensing port adjacent to an anterior portion of the dentalcavity, such that when the device body is positioned within a mouth thedental cavity is adjacent to the teeth and the dispensing port isadjacent to a posterior surface of teeth such that the stimulant leavingthe dispensing port draws the tongue adjacent or next to the posteriorsurface of the teeth; and a fluid reservoir fluidly coupled to thedispensing port and configured to contain and supply the stimulant tothe dispensing port.

50. Another embodiment is the device of embodiment 49, wherein thedevice is further configured to allow for an intermittent change in thedelivery of the stimulant from the reservoir to the mouth through thedispensing port.

51. Another embodiment is the device of embodiment 50, furthercomprising: a valve located in a fluid path between the fluid reservoirand the dispensing port; and wherein the valve is configured to allowintermittently changing the delivery profile of the stimulant throughthe dispensing port.

52. Another embodiment is the device of embodiment 49, furthercomprising a palatial nesting section adjacent to the dental cavity andconfigured to nest within an arch of a palate to improve retention ofthe device body within the mouth.

53. Another embodiment is the device of embodiment 49, furthercomprising: a control unit configured to control the intermittentlychanged delivery of the stimulant.

54. Another embodiment is the device of embodiment 53, wherein: thecontrol unit is in coupled communication with the valve; and the controlunit comprises a user interface to control operation of the valve.

55. Another embodiment is the device of embodiment 51, furthercomprising: at least one sensor electrically coupled to the valve; andwherein the sensor is configured to generate a triggering signal.

56. Another embodiment is the device of embodiment 55, wherein thesensor comprises a pressure sensor, an optical sensor, a sound sensor, amovement sensor, an EEG sensor, an EMG sensor, or an electro-magneticsensor.

57. Another embodiment is the device of embodiment 55, wherein thesensor is coupled to the device body in a manner such that it is locatedwithin the mouth when the device body is positioned in the mouth.

58. Another embodiment is the device of embodiment 57, wherein thesensor is attached to the device body.

59. Another embodiment is the device of embodiment 55, wherein thesensor is spaced from the device body such that the sensor can remainexternal to the mouth when the device body is positioned in the mouth.

60. Another embodiment is a method for improving sleep quality in asleeping individual, comprising: providing a stimulant that induces anatural response within the mouth of the individual when in contact witha tongue of the individual; delivering the stimulant to the tongue in amanner configured to induce the natural response; temporarily reducingdelivery of the stimulant in a manner configured to temporarily reduceinducing the natural response; and returning to increased delivery ofthe stimulant to again induce the natural response.

61. Another embodiment is the method of embodiment 60, whereintemporarily reducing delivery of the stimulant comprises ceasingdelivery of the stimulant.

62. Another embodiment is the method of embodiment 61, wherein returningto increased delivery of the stimulant comprises restarting delivery ofthe stimulant.

63. Another embodiment is the method of embodiment 60, furthercomprising: limiting the amount of stimulant delivered to produce thebiologic activity resulting in reducing vibrations of a soft palate oruvula without waking the individual.

64. Another embodiment is an oral device for producing a biologicalresponse within the mouth to reduce sleep disorder breathing in anindividual, comprising: a device body having a dental cavity forremovably nesting with one or more structures within the mouth; and adispensing surface adjacent to an anterior portion of the dental cavity,such that when the device body is positioned within a mouth the dentalcavity is adjacent to the teeth and the dispensing surface is adjacentto a posterior surface of the teeth, where the dispensing surfacecomprises a supply of a stimulant, where the stimulant is releasablefrom the dispensing surface over a period of time and draws a tongueadjacent to or next to the posterior surface of the teeth.

65. Another embodiment is a medical device system for delivering atherapy to a mouth or tongue of a subject, comprising: an oral deviceconfigured to be secured within the mouth in a secured configuration; atherapy coupled to the oral device; wherein the oral device in thesecured configuration is configured to deliver the therapy into themouth; and at least one of:

the oral device in the secured configuration is configured to deliverthe therapy at an anterior location within the mouth,

the therapy comprises a source of therapeutic agent which is located atan external position outside of the mouth, and a delivery assembly iscoupled to the source and also to the oral device and is configured todeliver the agent from the source in the external position to the oraldevice in the secured configuration, an active controller is configuredto actively control a delivery profile of the therapy into the mouth viathe oral device,

a sensor is coupled to a sensor location on the oral device,

the oral device comprises a palatal bridge-less mouthpiece with a dentalcavity configured to nest on at least one tooth in the mouth; and

a coating deposited on a dispensing surface of the oral device at adelivery location, the therapy comprises a therapeutic agent containedwithin the coating, and the coating is configured to release thetherapeutic agent into the mouth at the delivery location.

66. Another embodiment is the system of embodiment 65, wherein the oraldevice in the secured configuration is configured to deliver the therapyat an anterior location within the mouth,

67. Another embodiment is the system of embodiment 66, wherein: thetherapy comprises a source of therapeutic agent which is located at anexternal position outside of the mouth; and a delivery assembly iscoupled to the source and also to the oral device and is configured todeliver the agent from the source in the external position to the oraldevice in the secured configuration.

68. Another embodiment is the system of embodiment 67, furthercomprising: an active controller that is configured to actively controla delivery profile of the therapy into the mouth via the oral device.

69. Another embodiment is the system of embodiment 68, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

70. Another embodiment is the system of embodiment 69, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

71. Another embodiment is the system of embodiment 68, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

72. Another embodiment is the system of embodiment 67, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

73. Another embodiment is the system of embodiment 72, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

74. Another embodiment is the system of embodiment 67, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

75. Another embodiment is the system of embodiment 66, furthercomprising: an active controller that is configured to actively controla delivery profile of the therapy into the mouth via the oral device atthe anterior location.

76. Another embodiment is the system of embodiment 65, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

77. Another embodiment is the system of embodiment 76, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

78. Another embodiment is the system of embodiment 75, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

79. Another embodiment is the system of embodiment 66, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

80. Another embodiment is the system of embodiment 79, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

81. Another embodiment is the system of embodiment 66, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

82. Another embodiment is the system of embodiment 65, wherein: thetherapy comprises a source of therapeutic agent that is located at anexternal position outside of the mouth; and a delivery assembly iscoupled to the source and also to the oral device and is configured todeliver the agent from the source in the external position to the oraldevice in the secured configuration.

83. Another embodiment is the system of embodiment 82, furthercomprising: an active controller that is coupled to the deliveryassembly and is configured to actively control a delivery profile of thedelivered agent into the mouth via the delivery assembly and oraldevice.

84. Another embodiment is the system of embodiment 83, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

85. Another embodiment is the system of embodiment 84, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

86. Another embodiment is the system of embodiment 83, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

87. Another embodiment is the system of embodiment 82, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

88. Another embodiment is the system of embodiment 87, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

89. Another embodiment is the system of embodiment 82, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

90. Another embodiment is the system of embodiment 65, furthercomprising: an active controller that is configured to actively controla delivery profile of the therapy into the mouth via the oral device.

91. Another embodiment is the system of embodiment 90, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

92. Another embodiment is the system of embodiment 91, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

93. Another embodiment is the system of embodiment 90, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

94. Another embodiment is the system of embodiment 65, furthercomprising: a sensor that is coupled to a sensor location on the oraldevice.

95. Another embodiment is the system of embodiment 94, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

96. Another embodiment is the system of embodiment 65, wherein: the oraldevice comprises a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

97. A medical device system for delivering a therapy to a mouth ortongue of a subject, comprising: a tongue position stimulator (TST)assembly configured to deliver a stimulus to the tongue so as tostimulate the tongue into a position; and a tongue position sensor (TSE)assembly configured to sense a location of the tongue at the position.

98. Another embodiment is the system of embodiment 97, furthercomprising: an oral device configured to be secured within the mouth ina secured configuration; wherein the TST comprises a stimulus coupled tothe oral device at a delivery location, and is configured to deliver thestimulus to the mouth or tongue in the secured configuration so as tostimulate the tongue to the position; and wherein the TSE comprises asensor coupled to the oral device at a sensor location and configured tosense a tongue position corresponding with the sensor location.

99. Another embodiment is the system of embodiment 98, furthercharacterized by at least one of:

the TST assembly is configured to deliver the stimulus into the mouth atan anterior location within the mouth via the oral device in the securedconfiguration;

the TST assembly further comprises a source of therapeutic agent whichcomprises a stimulant, and a delivery assembly configured to couple tothe source at an external location outside the mouth and also to theoral device in the secured configuration, and is configured to deliverthe agent from the source at the external location to the oral device inthe secured configuration in the mouth;

the TST assembly comprises an active controller that is configured toactively control a delivery profile of the delivered agent into themouth via the oral device; and

the oral device comprises a palatal bridge-less mouthpiece with a dentalcavity configured to nest on at least one tooth in the mouth.

100. Another embodiment is the system of embodiment 99, wherein: the TSTassembly is configured to deliver the therapy into the mouth at ananterior location within the mouth via the oral device in the securedconfiguration.

101. Another embodiment is the system of embodiment 99, wherein the TSTassembly further comprises: a source of therapeutic agent whichcomprises a stimulant; and a delivery assembly configured to couple tothe source at an external location outside the mouth and also to theoral device in the secured configuration, and is configured to deliverthe agent from the source at the external location to the oral device inthe secured configuration in the mouth.

102. Another embodiment is the system of embodiment 99, wherein the TSTassembly further comprises: an active controller that is configured toactively control a delivery profile of the delivered agent into themouth via the oral device.

103. Another embodiment is the system of embodiment 99, wherein the oraldevice comprises: a palatal bridge-less mouthpiece with a dental cavityconfigured to nest on at least one tooth in the mouth.

104. Other embodiments comprise the systems of any one of embodiments65-103, wherein the oral device is configured to be permanently orsemi-permanently implanted in the secured configuration in the mouth.

105. Other embodiments comprise the systems of any one of embodiments65-103, wherein the oral device is configured to be temporarilyimplanted in the secured configuration mouth and is removable from thesecured configuration.

106. Other embodiments comprise the systems of any one of embodiments65-103, wherein the oral device comprises a mouthpiece with at least onewall defining at least one dental cavity that is configured to nest onat least one tooth in the mouth.

107. Another embodiment is the system of embodiment 106, wherein themouthpiece comprises at least two opposite walls with a spacetherebetween, said space defining at least in part the dental cavity.

108. Another embodiment is the system of embodiment 106, wherein the atleast one dental cavity is configured to nest on multiple teeth in themouth.

109. Another embodiment is the system of embodiment 108, wherein themouthpiece is molded to form-fit onto the teeth of the subject.

110. Another embodiment is the system of embodiment 106, wherein the atleast one tooth comprises an incisor.

111. Another embodiment is the system of any one of embodiments 65-103,wherein: the therapy comprises a source of therapeutic agent; a firstdelivery port is located at a first port location on the oral devicecoinciding at or adjacent to an incisor in the secured configuration;and the therapeutic agent is coupled for delivery into the mouth at thefirst delivery port.

112. Another embodiment is the system of embodiment 111, wherein thefirst port location coincides at or adjacent to at least one of the twomiddle incisors in the front of the mouth.

113. Another embodiment is the system of embodiment 111, wherein: thesource comprises a reservoir; the therapeutic agent comprises a volumeof a fluid material; and a delivery tube is fluidly coupled to thereservoir and also to the delivery port so as to provide for fluiddelivery of the fluid material from the reservoir to the delivery port.

114. Other embodiments comprise the systems of any one of embodiments65-103, wherein the therapy comprises a stimulant.

115. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a delivered energy.

116. Another embodiment is the system of embodiment 115, wherein thedelivered energy comprises electricity.

117. Another embodiment is the system of embodiment 116, wherein thedelivered energy comprises an RF current.

118. Another embodiment is the system of embodiment 115, wherein thedelivered energy comprises thermal energy.

119. Another embodiment is the system of embodiment 115, wherein thedelivered energy comprises light energy.

120. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a cryogenic cooling stimulant.

121. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a material.

122. Another embodiment is the system of embodiment 121, wherein thematerial comprises a fluid.

123. Another embodiment is the system of embodiment 122, wherein thefluid comprises a liquid.

124. Another embodiment is the system of embodiment 122, wherein thefluid comprises a gas.

125. Another embodiment is the system of embodiment 121, wherein thematerial comprises a flavor.

126. Another embodiment is the system of embodiment 121, wherein thematerial comprises a taste.

127. Another embodiment is the system of embodiment 121, wherein thematerial comprises a smell.

128. Another embodiment is the system of embodiment 121, wherein thematerial comprises a liquid taste stimulant.

129. Another embodiment is the system of embodiment 121, wherein thematerial comprises a sweet taste.

130. Another embodiment is the system of embodiment 129, wherein thesweet taste comprises a sugar, or a pre-cursor, analog, or derivativethereof.

131. Another embodiment is the system of embodiment 130, wherein thesugar comprises xylitol, or a pre-cursor, analog, or derivative thereof.

132. Another embodiment is the system of embodiment 130, wherein thematerial comprises a liquid.

133. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a mechanical stimulant.

134. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a texture stimulant.

135. Another embodiment is the system of embodiment 114, wherein thestimulant comprises a tongue stimulant characterized as stimulating atongue repositioning activity in response to exposure to the stimulant.

136. Other embodiments include the systems of any of embodiments 65-66,75-81, 90-98, or 100-103, wherein: the therapy comprises a source oftherapeutic agent; the source comprises a reservoir; and the therapeuticagent comprises a therapeutic material within the reservoir.

137. Another embodiment is the system of embodiment 136, wherein: thereservoir is located in the oral device.

138. Another embodiment is the system of embodiment 136, wherein: thereservoir is located separately from the oral device at an externallocation outside the mouth when the oral device is in the securedconfiguration; and a delivery assembly is coupled to the reservoir andalso to the oral device and is configured to deliver the therapeuticmaterial from the reservoir in the external location to the mouth viathe oral device in the secured configuration.

139. Other embodiments include the systems of any of embodiments 65-103,wherein: the therapy comprises a source of therapeutic agent; and theactive controller comprises a pump coupled to a reservoir containing thetherapeutic agent and that is configured to pump the agent according tothe controlled delivery profile into the mouth via the oral device.

140. Other embodiments include the systems of any of embodiments 65-103,wherein the controlled delivery profile comprises a constant deliveryrate of the therapy over a time period.

141. Another embodiment is the system of embodiment 140, wherein thetime period is configured to coincide with a sleep period for thesubject.

142. Other embodiments include the systems of any one of embodiments65-103, wherein the controlled delivery profile comprises a changingdelivery rate of the therapy over time between at least a first rate anda second rate that is below the first rate.

143. Another embodiment is the system of embodiment 142, wherein thetime period is configured to coincide with a sleep period for thesubject.

144. Another embodiment is the system of embodiment 142, wherein thechanging delivery rate comprises a cycle between the first and secondrates over the time.

145. Another embodiment is the system of embodiment 144, wherein thefirst and second rates comprise on and off conditions.

146. Another embodiment is the system of embodiment 145, wherein the onand off conditions are relative to a threshold for achieving atherapeutic result in the subject, such that the first rate comprisingthe on condition is above the threshold, and the second rate comprisingthe off condition is below the threshold.

147. Another embodiment is the system of embodiment 146, wherein thesecond rate comprising the off condition comprises a substantially zerorate and non-delivery of the therapy.

148. Another embodiment is the system of embodiment 146, wherein thesecond rate comprising the off condition comprises a non-zero rate ofdelivering the therapy below the threshold.

149. Another embodiment is the system of embodiment 144, wherein thecycle comprises a substantial step cycle between the first and secondrates.

150. Another embodiment is the system of embodiment 145, wherein thecycle comprises a ramping cycle between the first and second rates.

151. Other embodiments include the systems of any of embodiments 65-103,wherein the active controller further comprises: a driver for drivingthe delivery of the therapy to the oral device; an input set ofinstructions for controlling the delivery according to the controlleddelivery profile, and a processor configured to receive the input set ofinstructions and coupled to the driver to actuate the driver to drivethe delivery of the therapy according to the instructions.

152. Another embodiment is the system of embodiment 151, wherein theprocessor is configured to receive the set of instructions at least inpart by a manual input by a user of the system.

153. Another embodiment is the system of embodiment 151, furthercomprising: a software program embedded in a non-transitory computerreadable medium that contains the at least a portion of the set ofinstructions; wherein the processor is configured to run the softwareprogram to receive at least the portion of the set of instructions.

154. Another embodiment is the system of embodiment 153, wherein theactive controller further comprises a sensor input configured to receivesensed information from a sensor coupled to the subject, and the set ofinstructions are variable in response to the sensed informationreceived.

155. Another embodiment is the system of embodiment 154, wherein thesensed information relates to a tongue position in the mouth of thesubject.

156. Other embodiments include the systems of any of embodiments 65-103,further comprising: a light source optically coupled to transmit anillumination light signal into the mouth at an illumination port on theoral device; and wherein the sensor comprises an optical sensorconfigured to sense a reflected light signal reflected in the mouth fromthe illumination light signal transmitted into the mouth.

157. Another embodiment is the system of embodiment 156, wherein thesensor is configured to sense a position of the tongue against thesensor location based at least in part upon a change in light from thelight source that is reflected from the first end.

158. Other embodiments include the systems of any of embodiments 65-103,wherein the sensor comprises a pressure sensor.

159. Another embodiment is the system of embodiment 158, wherein thepressure sensor comprises an optical pressure sensor.

160. Another embodiment is the system of embodiment 158, wherein thepressure sensor comprises a pneumatic or hydraulic pressure sensor.

161. Another embodiment is the system of embodiment 158, wherein thepressure sensor comprises a strain gauge pressure sensor.

162. Other embodiments include the systems of any of embodiments 65-103,wherein the sensor is configured to sense a position of the tongue inthe mouth.

163. Another embodiment is the system of embodiment 162, wherein theposition comprises an anterior portion of the mouth.

164. Another embodiment is the system of embodiment 163, wherein theanterior position is at or adjacent to the front incisors in the mouth.

165. Another embodiment is the system of embodiment 164, wherein theanterior position is at or adjacent to the front top incisors in themouth.

166. Other embodiments include the systems of any of embodiments 65-103,wherein the sensor is configured to sense an applied force at the sensorlocation.

167. Another embodiment is the system of embodiment 166, wherein thesensor location is on a lingual side of the teeth, and the applied forceis from the tongue.

168. Other embodiments include the system of any of embodiments 65-103,wherein: the oral device comprises a mouthpiece with at least one dentalcavity configured to nest on multiple teeth in the mouth comprising atleast the two middle front incisors; the source of therapeutic agentcomprises a reservoir containing a volume of fluid flavor, taste, orsmell stimulant; the delivery assembly comprises a fluid delivery tubethat is fluidly coupled to the reservoir at the external locationoutside of the mouth and also to a delivery port located at a deliveryport location on the mouthpiece coinciding with at least one of theincisor teeth in the secured configuration; and the active controllercomprises a pump configured to actively control a delivery profile ofthe stimulant from the reservoir via the delivery assembly to themouthpiece and through the delivery port into the mouth.

169. Another embodiment is the system of embodiment 168, and furtherwherein; the therapy comprises a stimulated repositioning of the tongueto the anterior location in response to the controlled delivery of thestimulant into the mouth.

170. Another embodiment is a method for delivering a therapy to a mouthor tongue of a subject, comprising: securing an oral device within themouth in a secured configuration; coupling a therapy to the oral device;delivering the therapy into the mouth via the oral device; and at leastone of:

delivering the therapy at an anterior location within the mouth via theoral device in the secured configuration,

providing a source of a therapeutic agent at an external positionoutside of the mouth, coupling the source in the external position tothe oral device in the secured configuration via a delivery assembly,and delivering the agent from the source in the external position to theoral device in the secured configuration via the delivery assembly,

actively controlling a delivery profile of the therapy into the mouthvia the oral device in the secured configuration,

sensing a parameter within the mouth with a sensor at a sensor locationon the oral device in the secured configuration;

securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth; and

coupling the therapy to the oral device by coating a therapeutic agentonto a dispensing surface of the oral device, and delivering the therapyinto the mouth by releasing the therapeutic agent into the mouth via thecoating.

171. Another embodiment is the method of embodiment 170, furthercomprising: delivering the therapy at an anterior location within themouth via the oral device in the secured configuration.

172. Another embodiment is the method of embodiment 171, furthercomprising: positioning a source of therapeutic agent at an externalposition outside of the mouth; and coupling the source to the oraldevice in the secured configuration via a delivery assembly; anddelivering the therapy by delivering the agent from the source in theexternal position to the oral device in the secured configuration viathe delivery assembly.

173. Another embodiment is the method of embodiment 172, furthercomprising: actively controlling a delivery profile of the therapy intothe mouth via the oral device in the secured configuration.

174. Another embodiment is the method of embodiment 173, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

175. Another embodiment is the method of embodiment 174, furthercomprising: securing the oral device in the secured configuration bynesting a dental cavity of a palatal bridge-less mouthpiece on at leastone tooth in the mouth.

176. Another embodiment is the method of embodiment 173, furthercomprising: securing the oral device in the secured configuration bynesting a dental cavity of a palatal bridge-less mouthpiece on at leastone tooth in the mouth.

177. Another embodiment is the method of embodiment 172, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

178. Another embodiment is the method of embodiment 177, furthercomprising: securing the oral device in the secured configuration bynesting a dental cavity of a palatal bridge-less mouthpiece on at leastone tooth in the mouth.

179. Another embodiment is the method of embodiment 172, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

180. Another embodiment is the method of embodiment 171, furthercomprising: actively controlling a delivery profile of the therapy intothe mouth via the oral device in the secured configuration.

181. Another embodiment is the method of embodiment 170, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

182. Another embodiment is the method of embodiment 181, furthercomprising: securing the oral device in the secured configuration bynesting a dental cavity of a palatal bridge-less mouthpiece on at leastone tooth in the mouth.

183. Another embodiment is the method of embodiment 180, furthercomprising: securing the oral device in the secured configuration bynesting a dental cavity of a palatal bridge-less mouthpiece on at leastone tooth in the mouth.

184. Another embodiment is the method of embodiment 171, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

185. Another embodiment is the method of embodiment 184, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

186. Another embodiment is the method of embodiment 171, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

187. Another embodiment is the method of embodiment 170, wherein:

positioning a source of therapeutic agent at an external positionoutside of the mouth; and coupling the source to the oral device in thesecured configuration via a delivery assembly; and delivering thetherapy by delivering the agent from the source in the external positionto the oral device in the secured configuration via the deliveryassembly.

188. Another embodiment is the method of embodiment 187, furthercomprising: actively controlling a delivery profile of the therapy intothe mouth via the oral device in the secured configuration.

189. Another embodiment is the method of embodiment 188, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

190. Another embodiment is the method of embodiment 189, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

191. Another embodiment is the method of embodiment 188, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

192. Another embodiment is the method of embodiment 187, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

193. Another embodiment is the method of embodiment 192, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

194. Another embodiment is the method of embodiment 187, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

195. Another embodiment is the method of embodiment 170, furthercomprising: actively controlling a delivery profile of the therapy intothe mouth via the oral device in the secured configuration.

196. Another embodiment is the method of embodiment 195, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

197. Another embodiment is the method of embodiment 196, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

198. Another embodiment is the method of embodiment 195, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

199. Another embodiment is the method of embodiment 170, furthercomprising: sensing a parameter within the mouth with a sensor at asensor location on the oral device in the secured configuration.

200. Another embodiment is the method of embodiment 199, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

201. Another embodiment is the method of embodiment 170, wherein:securing the oral device in the secured configuration by nesting adental cavity of a palatal bridge-less mouthpiece on at least one toothin the mouth.

202. A method for delivering a therapy to a mouth or tongue of asubject, comprising: delivering a stimulus to the tongue via a tongueposition stimulator (TST) assembly; stimulating the tongue into aposition by delivering the stimulus; and sensing a location of thetongue at the position via a tongue position sensor (TSE) assembly.

203. Another embodiment is the method of embodiment 202, furthercomprising: securing an oral device within the mouth in a securedconfiguration; wherein the TST assembly delivers the stimulus at adelivery location on the oral device in the secured configuration; andwherein the TSE assembly senses the tongue location at the position viaa sensor coupled to the oral device at a sensor location correspondingwith the position in the secured configuration.

204. Another embodiment is the method of embodiment 203, whereindelivering the stimulus via the TST is further characterized by at leastone of:

delivering the stimulus at an anterior location within the mouth via theoral device in the secured configuration;

coupling a source of therapeutic agent comprising a stimulant at anexternal location outside the mouth to the oral device in the securedconfiguration via a delivery assembly, and delivering the agent with thedelivery assembly from the source at the external location and to theoral device in the secured configuration and into the mouth;

actively controlling a delivery profile of the delivered agent into themouth via the oral device in the secured configuration;

securing the oral device in the secured configuration by nesting dentalcavity of a palatal bridge-less mouthpiece on at least one tooth in themouth; and

coating the therapeutic agent onto a dispensing surface of the oraldevice, and releasing the therapeutic agent from the coating into themouth.

205. Another embodiment is the method of embodiment 204, whereindelivering the stimulus via the TST is further characterized by:delivering the stimulus at an anterior location within the mouth via theoral device in the secured configuration.

206. Another embodiment is the method of embodiment 204, whereindelivering the stimulus via the TST is further characterized by:coupling a source of therapeutic agent comprising a stimulant at anexternal location outside the mouth to the oral device in the securedconfiguration via a delivery assembly; and delivering the agent with thedelivery assembly from the source at the external location and to theoral device in the secured configuration and into the mouth.

207. Another embodiment is the method of embodiment 204, whereindelivering the stimulus via the TST is further characterized by:actively controlling a delivery profile of the delivered agent into themouth via the oral device in the secured configuration.

208. Another embodiment is the method of embodiment 204, whereindelivering the stimulus via the TST is further characterized by:securing the oral device in the secured configuration by nesting dentalcavity of a palatal bridge-less mouthpiece on at least one tooth in themouth.

209. Other embodiments include the methods of any of embodiments170-208, further comprising: permanently or semi-permanently implantingthe oral device in the secured configuration in the mouth.

210. Other embodiments include the methods of any of embodiments170-208, further comprising: removably securing the oral device in thesecured configuration during a sleep period; and removing the removablysecured oral device from the secured configuration following terminationof the sleep period.

211. Other embodiments include the methods of any of embodiments170-208, further comprising: securing the oral device in the securedconfiguration in the mouth by nesting at least one wall defining atleast one dental cavity on at least one tooth in the mouth.

212. Another embodiment is the method of embodiment 211, furthercomprising: positioning the at least one tooth within at least one spacebetween at least two opposite walls defining at least in part the dentalcavity.

213. Another embodiment is the method of embodiment 211, furthercomprising nesting the at least one wall defining the at least onedental cavity on multiple teeth in the mouth.

214. Another embodiment is the method of embodiment 213, furthercomprising molding a mouthpiece to form-fit onto the multiple teeth.

215. Another embodiment is the method of embodiment 211, wherein the atleast one tooth comprises an incisor.

216. Another embodiment is the method of any one of embodiments 170-208above, wherein delivering the therapy via the TST assembly is furthercharacterized by: providing a source of therapeutic agent; positioning afirst delivery port that is located at a first port location on the oraldevice to coincide at or adjacent to an incisor in the securedconfiguration; and coupling the therapeutic agent to the first deliveryport and delivering the agent through the first delivery port at thefirst port location in the secured configuration.

217. Another embodiment is the method of embodiment 216, furthercomprising: positioning the first port location to coincide at oradjacent to at least one of the two middle incisors in the front of themouth in the secured configuration.

218. Another embodiment is the method of embodiment 216, whereindelivering the therapy via the TST is further characterized by:providing the source of therapeutic agent in a reservoir; providing thetherapeutic agent as a volume of a fluid material; and fluidly couplingthe reservoir to the delivery port via a delivery passagewaytherebetween; and causing the fluid material to flow from the reservoir,along the delivery passageway, and through the delivery port into themouth.

219. Other embodiments include the methods of any of embodiments170-208, wherein delivering the therapy comprises delivering astimulant.

220. Another embodiment is the method of embodiment 219, wherein thedelivering the stimulant comprises delivering energy.

221. Another embodiment is the method of embodiment 220, whereindelivering the energy comprises delivering an electrical current.

222. Another embodiment is the method of embodiment 221, wherein thedelivered the electrical current comprises delivering a radiofrequency(RF) current.

223. Another embodiment is the method of embodiment 220, whereindelivering the energy comprises delivering thermal energy.

224. Another embodiment is the method of embodiment 220, whereindelivering the energy comprises delivering light energy.

225. Another embodiment is the method of embodiment 219, whereindelivering the stimulant comprises delivering a cryogenic coolingstimulant.

226. Another embodiment is the method of embodiment 219, whereindelivering the stimulant comprises delivering a material.

227. Another embodiment is the method of embodiment 226, wherein thedelivering the material comprises delivering a fluid.

228. Another embodiment is the method of embodiment 227, whereindelivering the fluid comprises delivering a liquid.

229. Another embodiment is the method of embodiment 227, whereindelivering the fluid comprises delivering a gas.

230. Another embodiment is the method of embodiment 226, whereindelivering the material comprises delivering a flavor.

231. Another embodiment is the method of embodiment 226, whereindelivering the material comprises delivering a taste.

232. Another embodiment is the method of embodiment 226, whereindelivering the material comprises delivering a smell.

233. Another embodiment is the method of embodiment 226, whereindelivering the material comprises delivering a liquid taste stimulant.

234. Another embodiment is the method of embodiment 226, whereindelivering the material comprises delivering a sweet taste.

235. Another embodiment is the method of embodiment 234, whereindelivering the sweet taste comprises delivering a sugar, or apre-cursor, analog, or derivative thereof.

236. Another embodiment is the method of embodiment 235, whereindelivering the sugar comprises delivering xylitol, or a pre-cursor,analog, or derivative thereof.

237. Another embodiment is the method of embodiment 235, whereindelivering the material comprises delivering a liquid.

238. Another embodiment is the method of embodiment 219, wherein thedelivering the stimulant comprises providing a mechanical stimulant.

239. Another embodiment is the method of embodiment 219, whereindelivering the stimulant comprises delivering a texture stimulant.

240. Another embodiment is the method of embodiment 219, whereindelivering the stimulant comprises delivering a tongue stimulantcharacterized as stimulating a tongue repositioning activity in responseto exposure to the stimulant.

241. Another embodiment is a method of any one of embodiments 170-171,180-186, 195-203, or 205-208 above, further comprising: providing asource of therapeutic agent which comprises a therapeutic material in areservoir; delivering the therapy is further characterized by deliveringthe therapeutic material from the reservoir into the mouth via the oraldevice in the secured configuration.

242. Another embodiment is the method of embodiment 241, furthercomprising: positioning the reservoir in the oral device and in themouth in the secured configuration.

243. Another embodiment is the method of embodiment 241, furthercomprising: positioning the reservoir to be located separately from theoral device at an external location outside the mouth when the oraldevice is in the secured configuration; and using a delivery assembly tocouple the externally positioned reservoir to the oral device, and todeliver the therapeutic material from the reservoir in the externallocation to the mouth via the oral device, while the oral device is inthe secured configuration.

244. Other embodiments include the methods of any of embodiments170-208, further comprising: providing the therapy to comprise a sourceof therapeutic agent in a reservoir; and coupling a pump to an activecontroller and also to the reservoir; actively controlling the pump viathe active controller to deliver the agent with a controlled deliveryprofile from the reservoir and to the oral device in the securedconfiguration and into the mouth.

245. Other embodiments include the methods of any of embodiments170-208, further comprising: delivering the therapy with a controlleddelivery profile which comprises a constant delivery rate of the therapyover a time period.

246. Another embodiment is the method of embodiment 245, furthercomprising configuring the time period to coincide with a sleep periodfor the subject.

247. Other embodiments include the methods of any of embodiments170-208, further comprising: delivering the therapy with a controlleddelivery profile that comprises a changing delivery rate of the therapyover time between at least a first rate and a second rate that is belowthe first rate.

248. Another embodiment is the method of embodiment 247, furthercomprising configuring the time period to coincide with a sleep periodfor the subject.

249. Another embodiment is the method of embodiment 247, furthercomprising configuring the changing delivery rate to comprise a cyclebetween the first and second rates over the time.

250. Another embodiment is the method of embodiment 249, furthercomprising configuring the first and second rates to comprise on and offconditions, respectively.

251. Another embodiment is the method of embodiment 250, furthercomprising configuring the on and off conditions relative to a therapydelivery threshold for achieving a therapeutic result in the subject,such that the first rate comprising the on condition is configured tocomprise delivering the therapy above the threshold, and the second ratecomprising the off condition is configured to comprise delivering thetherapy below the threshold.

252. Another embodiment is the method of embodiment 251, wherein the offcondition of the second rate comprises a substantially zero rate andnon-delivery of the therapy.

253. Another embodiment is the method of embodiment 251, wherein the offcondition of the second rate comprises a non-zero rate of therapydelivery that is below the threshold.

254. Another embodiment is the method of embodiment 249, wherein thecycle comprises a substantial step cycle between the first and secondrates.

255. Another embodiment is the method of embodiment 250, wherein thecycle comprises a ramping cycle between the first and second rates.

256. Other embodiments include the methods of any of embodiments170-208, wherein actively controlling the therapy delivery is furthercharacterized by: using a driver for driving the delivery of the therapyto the oral device; providing an input set of instructions forcontrolling the delivery according to the controlled delivery profile,configuring a processor to receive the input set of instructions; andcoupling the processor to the driver to actuate the driver to drive thedelivery of the therapy according to the instructions.

257. Another embodiment is the method of embodiment 256, furthercomprising manually inputting the instructions to the processor.

258. Another embodiment is the method of embodiment 256, furthercomprising: providing a software program embedded in a non-transitorycomputer readable medium and that comprises at least a portion of theset of instructions; and configuring the processor to run the softwareprogram to receive at least the portion of the set of instructions.

259. Another embodiment is the method of embodiment 258, furthercomprising providing or receiving sensed information from a sensorcoupled to the subject, and varying the set of instructions in responseto the sensed information received.

260. Another embodiment is the method of embodiment 259, wherein thesensed information relates to a tongue position in the mouth of thesubject.

261. Other embodiments include the methods of any of embodiments170-208, further comprising: transmitting a light signal into the mouthfrom a light source optically coupled to an illumination port on theoral device; and sensing a reflected light signal reflected in the mouthfrom the illumination light signal transmitted into the mouth via alight sensor at a sensor location on the oral device.

262. Another embodiment is the method of embodiment 261, wherein thesensing comprises sensing a position of the tongue against the sensorlocation based at least in part upon a change in light from the lightsource that is reflected at the sensor location.

263. Other embodiments include the methods of any of embodiments170-208, wherein the sensing comprises a sensing a pressure with apressure sensor.

264. Another embodiment is the method of embodiment 263, wherein thepressure sensor comprises an optical pressure sensor.

265. Another embodiment is the method of embodiment 263, wherein thepressure sensor comprises a pneumatic or hydraulic pressure sensor.

266. Another embodiment is the method of embodiment 263, wherein thepressure sensor comprises a strain gauge pressure sensor.

267. Other embodiments include the methods of any of embodiments170-208, further comprising sensing a position of the tongue in themouth.

268. Another embodiment is the method of embodiment 267, wherein theposition comprises an anterior portion of the mouth.

269. Another embodiment is the method of embodiment 268, wherein theanterior position is at or adjacent to the front incisors in the mouth.

270. Another embodiment is the method of embodiment 269, wherein theanterior position is at or adjacent to the front top incisors in themouth.

271. Other embodiments include the methods of any of embodiments170-208, further comprising sensing an applied force at a sensorlocation in the mouth.

272. Another embodiment is the method of embodiment 271, wherein thesensor location is on a lingual side of the teeth, and the applied forceis from the tongue.

273. Another embodiment is the method of any one of embodiments 170-208,further comprising: nesting at least one dental cavity of a mouthpieceof the oral device on multiple teeth comprising at least the two middlefront incisors in the mouth; providing a source of therapeutic agent tocomprise a volume of fluid flavor, taste, or smell stimulant material ina reservoir positioned at an external location outside of the mouth;using a fluid delivery tube to fluidly couple the reservoir at theexternal location outside of the mouth to a delivery port located at adelivery port location on the mouthpiece coinciding with at least one ofthe incisor teeth in the secured configuration; and actively controllingthe therapy delivery via a controlled pump with a delivery profile ofstimulant from the reservoir via the delivery assembly to the mouthpieceand through the delivery port into the mouth.

274. Another embodiment is the method of embodiment 273, whereindelivering the therapy further comprises; stimulating a repositioning ofthe tongue to the anterior location in response to the controlleddelivery of the stimulant into the mouth.

275. Another embodiment is a method of any of embodiments 170-208,further comprising: treating a sleep disorder with the therapy delivery.

276. Another embodiment is the method of embodiment 275, whereintreating the sleep disorder comprises treating obstructive sleep apneaor snoring with the therapy delivery.

277. Other embodiments include the method, device, and systemembodiments elsewhere herein described, but includes constant or nearconstant delivery of the fluid or material containing the stimulant, butdiluting or adjusting the stimulant in the fluid or material so that theresponse is insufficient to wake the individual. For example, in caseswhere the stimulant is a taste, smell, or flavor stimulant, thestimulant can be diluted in a solution where the concentration is heldhigh enough to cause the desired response but low enough to avoid wakingthe patient and is continuously delivered over a period of time. Thisstimulant concentration in the delivery vehicle (e.g. fluid or othermaterial), or conversely its dilution, may be varied over time to changethe stimulant component being delivered, and thus biologic stimulation,as considered consistent with and falling within the other aspects ofthe present disclosure exemplified by the detailed embodiments.

288. Another embodiment is a method for treating sleep disorderbreathing in a sleeping individual, the method comprising: providing astimulant that induces at least one natural response within a mouth ofthe sleeping individual when the stimulant enters the mouth; deliveringthe stimulant at a location posteriorly adjacent to one or more teeth inthe mouth to induce at least one natural response to reduce sleepdisorder breathing and improve the ability of the sleeping individual tomaintain a sleep state; and controlling delivery of the stimulant, wherecontrolling delivery prevents the stimulant from waking the individual.

289. Another embodiment is the method of embodiment 288, furthercomprising actively controlling the stimulant delivery with an activecontroller.

290. Another embodiment is a method for minimizing sleep disturbances inan individual, the method comprising: positioning a dispensing unitwithin a mouth of the individual, where the dispensing unit comprises atleast one port adjacent to a tongue; providing a supply of a stimulantthrough the port that induces a biological response in the mouth of theindividual; controlling delivery of the stimulant; and wherein thecontrolled delivery of the stimulant is configured to induce thebiological response without waking the individual.

291. Another embodiment is an oral dispensing device for dispensing astimulant that produces a biological response within a mouth or airwayto reduce sleep disorder breathing in an individual, the oral dispensingdevice comprising: a supply of a stimulant solution comprising astimulant at a concentration configured to cause a biological responsewhen the stimulant solution is delivered in the mouth above a thresholddelivery rate; a device body having a dental cavity for removablynesting with one or more structures within the mouth; a dispensing portadjacent to an anterior portion of the dental cavity, such that when thedevice body is positioned within a mouth the dental cavity is adjacentto the teeth and the dispensing port is adjacent to a posterior surfaceof teeth such that the stimulant solution leaving the dispensing portdraws the tongue adjacent or next to the posterior surface of the teeth;a fluid reservoir fluidly coupled to the dispensing port and configuredto maintain a supply of the stimulant solution; and wherein thestimulant in the stimulant solution is also diluted sufficiently toavoid waking the patient when continuously delivered over a period oftime.

292. Another embodiment is a method for causing a natural response in anindividual to maintain a sleep state, the method comprising: providing astimulant that induces a physiological response within a mouth, throat,or airway of the individual where the physiological response causes achange in the individual to maintain or improve a state of sleep;delivering the stimulant in the mouth to induce the physiologicalresponse; and controlling an amount of the stimulant that is deliveredto allow the individual to maintain the sleep state.

293. Another embodiment is the method of embodiment 292, whereindelivering the stimulant comprises delivering the stimulant at alocation behind one or more teeth in the mouth.

294. Another embodiment is a method for improving sleep for anindividual, the method comprising: providing a stimulant that induces aphysiological response within a mouth, throat, or airway of theindividual; delivering the stimulant at a location behind one or moreteeth in the mouth to induce the physiological response; and controllingan amount of the stimulant that is delivered to allow the individual tomaintain a sleep state.

295. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, wherein aphysiological response is stimulated which comprises a degree of tonguemovement and/or increased tongue muscle tone that is sufficient to openthe airway to reduce an incidence of sleep disorder breathing.

296. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, wherein aphysiological response is stimulated which comprises swallowing.

297. Another embodiment is the method, device, or system of embodiment296 above, wherein at least one of a rate or volume of fluid deliveryand a degree of stimulated salivation is sufficient to cause theindividual or subject to swallow.

298. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, wherein providingthe stimulant comprises automatically delivering the stimulant from asupply source while the individual is in the sleep state.

299. Another embodiment is the method, device, or system of any of theother embodiments elsewhere disclosed herein, such as for example thenumbered embodiments above or below, wherein a physiological response isstimulated that reduces vibrations of a soft palate or uvula withoutwaking the individual.

300. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, wherein providingthe stimulant includes positioning an oral appliance within the mouthhaving a delivery port that delivers the stimulant to the tongue.

301. Another embodiment is the method, device, or system of any of theother oral appliance embodiments elsewhere disclosed herein, such as forexample the numbered embodiments above or below, wherein positioning theoral appliance within the mouth comprises positioning the oral applianceon at least one of the lower front teeth such that the delivery port ofthe oral appliance is directly adjacent to the posterior side of theupper front teeth.

302. Another embodiment is the method, device, or system of any of theother oral appliance embodiments elsewhere disclosed herein, such as forexample the numbered embodiments above or below, wherein positioning theoral appliance within the mouth comprises positioning the oral applianceon at least one of the upper front teeth such that the delivery port ofthe oral appliance is directly adjacent to the posterior side of theupper front teeth.

303. Another embodiment is the method, device, or system of any of theother oral appliance embodiments elsewhere disclosed herein, such as forexample the numbered embodiments above or below, wherein the oralappliance comprises at least one of a mandibular advancement device, acontinuous positive airway pressure device, a mouthguard, a custommolded mouthpiece, and a retainer.

304. Another embodiment is the method, device, or system of any of theother oral appliance stimulant delivery embodiments elsewhere disclosedherein, such as for example the numbered embodiments above or below,where the oral appliance comprises an internal reservoir coupled to adispensing or delivery port, the internal reservoir containing at leasta portion of the stimulant.

305. Another embodiment is the embodiment 304 above, further comprisinga valve, wherein providing the stimulant comprises opening of the valveto dispense the stimulant.

306. Another embodiment is the embodiment of 305 above, wherein thedelivery port comprises the valve.

307. Another embodiment is the embodiment of 305 above, wherein thereservoir is fluidly coupled to the dispensing or delivery port, and thestimulant comprises a fluid.

308. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, where providing thestimulant comprises providing an external reservoir containing thestimulant.

309. Another embodiment is the method, device, or system of any of theother tongue position stimulation embodiments elsewhere disclosedherein, such as for example the numbered embodiments above or below,further comprising providing a second stimulant to trigger an olfactoryresponse in the sleeping individual.

310. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, where the stimulantcomprises a substance comprising at least one of a sour taste, a citrictaste, and a sweet taste.

311. Another embodiment is the method, device, or system of any of theother stimulant delivery embodiments elsewhere disclosed herein, such asfor example the numbered embodiments above or below, wherein thestimulant comprises xylitol.

312. Another embodiment is the method, device, or system of any of theother controlled stimulant delivery embodiments elsewhere disclosedherein, such as for example the numbered embodiments above or below,wherein controlling the amount of stimulant comprises intermittentlypausing delivery of the stimulant comprises pausing the stimulant untila triggering signal restarts delivery of the stimulant.

313. Another embodiment is the embodiment 312, further comprising usinga dispensing unit in electrical communication with a sensor assembly,wherein the triggering signal is generated in response to a sensedparameter that is sensed by a sensor of the sensor assembly.

314. Another embodiment is the method, device, or system of any of theother sensor embodiments elsewhere disclosed herein, such as for examplethe numbered embodiments above or below, wherein the sensor comprises apressure sensor, an optical sensor, a sound sensor, a movement sensor,or an electro-magnetic sensor.

315. Another embodiment is the method, device, or system of any of theother sensor embodiments elsewhere disclosed herein, such as for examplethe numbered embodiments above or below, wherein the sensor ispositioned in the mouth and generates a signal based on a movement orposition of the tongue.

316. Another embodiment is the method, device, or system of any of theother embodiments related to sensors, triggering signals, and controlleddelivery of stimulant as elsewhere disclosed herein, such as for examplethe numbered embodiments above or below, wherein the amount of stimulantdelivered is determined by the triggering signal.

317. Another embodiment is the method, device, or system of any of theother embodiments related to sensors, triggering signals, and controlleddelivery of stimulant as elsewhere disclosed herein, such as for examplethe numbered embodiments above or below, further comprising measuring adegree of tongue movement with the sensor and using the triggeringsignal to determine the amount of stimulant delivery based on the degreeof movement.

318. Another embodiment is the method, device, or system of any of theother embodiments related to sensors, triggering signals, and controlleddelivery of stimulant as elsewhere disclosed herein, such as for examplethe numbered embodiments above or below, wherein controlling delivery ofthe stimulant, including but not limited to intermittently pausingdelivery, are timed with an event or physiologic parameter related to orcomprising at least one of respiration, respiratory effect, respiratoryflow, hypoxia, hypopnea, oxygen saturation, pausing the stimulant untila triggering signal restarts delivery of the stimulant.

319. Another embodiment is the method, device, or system of any of theother embodiments related to therapeutic agent delivery via a fluidreservoir coupled to a dispensing port on an oral appliance, such as forexample the numbered embodiments above or below, wherein a valve isprovided which is located in a fluid path between the fluid reservoirand the dispensing port, and wherein the valve is adjustable to allowfor a variable dispensing rate of the stimulant through the dispensingport.

320. Another embodiment is the embodiment 319 above, wherein the valveis adjustable to allow for intermittent change in the delivery, such asfor example but not limited to intermittently pausing delivery, of thestimulant.

321. Another embodiment is any one of the preceding system embodimentsabove, to extent comprising a therapeutic agent provided on or withinthe oral device for delivery to the mouth in the secured configuration,and further comprising:

a coating deposited on a surface of the oral device at a deliverylocation; wherein the therapy comprises a therapeutic agent containedwithin the coating; and

wherein the coating is configured to release the therapeutic agent intothe mouth at the delivery location.

322. Another embodiment is embodiment 321 above, and wherein the coatingis deposited onto the dispensing surface via an ultraviolet (UV) lightlinking process.

323. Another embodiment is embodiment 321 above, and wherein the coatingis deposited onto the dispensing surface via a solvent-based deposition.

324. Another embodiment comprises the embodiment 321 above, and furthercomprising a capsule or film over the coating and configured to dissolveover sufficient time for the patient to fall asleep before thetherapeutic agent, such as a stimulant (such as a taste compound),starts to release into the mouth.

325. Another embodiment comprises the embodiment 324 above, comprisingmultiple alternating layers of the coating containing the therapeuticagent and the film, respectively.

326. Another embodiment comprises the embodiment 325 above, comprisingmultiple alternating layers of a coating comprising a taste compound andtasteless transition layers so that intermittent delivery of the tasteis accomplished as the alternating layers dissolve.

327. Another embodiment comprises any one of the preceding systemembodiments above, to extent comprising a therapeutic agent provided onor within the oral device for delivery to the mouth in the securedconfiguration, and further comprising a coating or capsule coupled tothe oral device and comprising multiple alternating dissolvable layersconfigured for elevated and reduced delivery of therapeutic agent,respectively.

328. Another embodiment comprises the embodiment 327 above, comprisingmultiple alternating layers of therapeutic agent and agent-lesstransition layers configured for intermittent delivery of thetherapeutic agent.

329. Another embodiment is any one of the preceding method embodimentsabove, comprising containing a therapeutic agent on or within the oraldevice for delivery to the mouth in the secured configuration, andfurther comprising:

coupling the therapy to the oral device by depositing a therapeuticagent in a surface coating on a dispensing surface of the oral device ata delivery location; and

delivering the therapy into the mouth via the oral device by releasingthe therapeutic agent into the mouth via the surface coating at thedelivery location.

330. Another embodiment is embodiment 329 above, and further comprisingdepositing the coating onto the dispensing surface via an ultraviolet(UV) light linking process.

331. Another embodiment is embodiment 329 above, and further comprisingdepositing the coating onto the dispensing surface via a solvent-baseddeposition.

332. Another embodiment comprises the embodiment 329 above, and furthercomprising a capsule or film deposited over the coating and configuredto dissolve in the mouth over sufficient time for the patient to fallasleep before the therapeutic agent, such as a stimulant (such as ataste compound), starts to release from the coating into the mouth.

333. Another embodiment comprises the embodiment 332 above, comprisingsequentially dissolving multiple alternating layers of the coatingcontaining the therapeutic agent and the film, respectively, over timeso as to control agent delivery to change over time.

334. Another embodiment comprises the embodiment 333 above, comprisingdissolving multiple alternating layers of the coating comprising a tastecompound and the film comprising tasteless transition layers, so thatintermittent delivery of the taste is accomplished as the alternatinglayers dissolve.

335. Another embodiment comprises any one of the preceding methodembodiments above and comprising providing a therapeutic agent on orwithin the oral device for delivery to the mouth in the securedconfiguration, and further comprising:

coupling a coating or capsule to the oral device and comprising multiplealternating dissolvable layers; and

allowing the alternating dissolvable layers to dissolve sequentiallyover time for elevated and reduced delivery of therapeutic agent,respectively, over time.

336. Another embodiment comprises the embodiment 335 above, wherein:

the multiple alternating layers comprise therapeutic agent andagent-less transition layers; and

dissolving the alternating layers sequentially over time allowsintermittent delivery of the therapeutic agent over time.

337. Another embodiment is any one of the embodiments above andcomprising delivery of a therapeutic agent into the mouth via the oraldevice, and wherein the therapeutic agent comprises a non-gaspreparation for delivery.

338. Another embodiment is any one of the system embodiments above, toextent related to delivering a therapy to an anterior portion of themouth, wherein the oral device in the secured configuration isconfigured to isolate local delivery of the therapy at only an anteriorlocation within the mouth at or adjacent to the front incisors.

339. Another embodiment is the system embodiment 338 above, used in anyone of the respective method embodiments above, wherein the methodfurther comprises locally delivering the therapy to only the anteriorportion of the mouth at or adjacent to the front incisors.

The above illustrations are examples of the invention described herein.Because of the scope of the invention, it is specifically contemplatedthat combinations of aspects of specific embodiments or combinations ofthe specific embodiments themselves are within the scope of thisdisclosure.

Although the description herein contains many details, these should notbe construed as limiting the scope of the invention but as merelyproviding illustrations of some of the presently preferred embodimentsof this invention. Therefore, it will be appreciated that the scope ofthe present invention fully encompasses other embodiments which maybecome obvious to those skilled in the art. Furthermore, reference to anelement in the singular is not intended to mean “one and only one”unless explicitly so stated, but rather “one or more.” All structural,chemical, and functional equivalents to the elements of theabove-described preferred embodiment that are known to those of ordinaryskill in the art are expressly incorporated herein by reference and areintended to be encompassed by the present disclosure and claims.Moreover, it is not necessary for a device or method to address each andevery problem sought to be solved by the present invention, for it to beencompassed by the present disclosure and claims. Furthermore, noelement, component, or method step in the present disclosure is intendedto be dedicated to the public regardless of whether the element,component, or method step is explicitly recited in the claims. No claimelement herein is to be construed under the provisions of 35 U.S.C. 112,sixth paragraph, unless the element is expressly recited using thephrase “means for.”

What is claimed is:
 1. A tongue position stimulator (TST) method fordelivering a stimulant to stimulate anterior repositioning of a tonguein a mouth of a subject in order to treat sleep disorder breathing,comprising: securing a dental retainer tray in a secured configurationonto a set of teeth comprising front incisors within the mouth and witha delivery port positioned at a delivery port location at or adjacent tothe front incisors; fluidly coupling a reservoir, located at an exteriorposition outside of the mouth and containing a source of the stimulantin a non-gas liquid preparation, to the delivery port via a deliveryassembly; delivering only the non-gas liquid preparation of stimulantfrom the reservoir in a locally isolated manner in its non-gas liquidform to only an anterior location within an anterior oral cavity at oradjacent to the front incisors within the mouth via the deliveryassembly and through the delivery port with the dental retainer tray inthe secured configuration; wherein the delivering is performed by usinga pump for actively controlling a delivery profile for pumping thenon-gas liquid preparation of stimulant via the delivery assembly intothe mouth at only the anterior location via the delivery port; andstimulating the anterior repositioning of the tongue freely toward thedelivery port and to the anterior location via the locally isolateddelivery of stimulant so as to thereby treat the sleep disorderbreathing.
 2. The method of claim 1, further comprising: controlling thedelivery profile according to a changing delivery rate of the stimulantdelivery, over a time period, between at least a first rate and a secondrate that is below the first rate.
 3. The method of claim 2, wherein thefirst rate comprises an on condition and the second rate comprises anoff condition.
 4. The method of claim 3, wherein the on and offconditions are relative to a threshold for achieving a therapeuticresult in the subject, such that the first rate comprising the oncondition is above the threshold, and the second rate comprising the offcondition is below the threshold.
 5. The method of claim 3, wherein thesecond rate comprising the off condition comprises a substantially zerorate and non-delivery of the stimulant.
 6. The method of claim 3,wherein the second rate comprising the off condition comprises anon-zero rate of delivering the stimulant below the threshold.
 7. Themethod of claim 2, further comprising: cycling the changing deliveryrate between the first and second rates over the time period.
 8. Themethod of claim 1, wherein the stimulant comprises a sweet flavor tastestimulant.
 9. The method of claim 8, wherein the sweet flavor tastestimulant comprises a sugar, or a pre-cursor, analog, or derivativethereof.
 10. The method of claim 9, wherein the sugar comprises xylitol,or a pre-cursor, analog, or derivative thereof.
 11. The method of claim1, wherein the actively controlling further comprises: using a processorto run a software program embedded in a non-transitory computer readablemedium to generate a set of control instructions from the softwareprogram in response to a set of input instructions received by theprocessor; and controlling the delivery profile of the non-gas liquidpreparation of stimulant via the pump via the set of controlinstructions.
 12. The method of claim 11, further comprising: coupling asensor to the dental retainer tray at a sensor location at or adjacentto the delivery port location; sensing information related to a tongueposition relative to the sensor location via the sensor in the securedconfiguration; and coupling the sensor to the processor to provide thesensed information as the set of input instructions.
 13. The method ofclaim 1, further comprising: controlling the delivery profile accordingto a constant delivery rate of the non-gas liquid preparation ofstimulant over a time period.
 14. The method of claim 13, furthercomprising: configuring the time period to coincide with a sleep periodfor the subject.
 15. The method of claim 1, wherein the dental retainertray comprises a set of multiple delivery ports that are positioned atmultiple respective delivery port locations at or adjacent to the frontincisors, and wherein said set includes the delivery port at thedelivery port location, and further comprising: fluidly coupling thereservoir to said multiple delivery ports at said multiple respectivedelivery port locations on the dental retainer tray coinciding at oradjacent to said front incisors in the secured configuration; anddelivering the non-gas liquid preparation of stimulant from thereservoir to the multiple respective delivery ports for delivery of thenon-gas liquid preparation of stimulant into the mouth at the multiplerespective delivery port locations.
 16. The method of claim 1, whereinsaid front incisors comprise two middle incisors, and furthercomprising: positioning the port location to coincide at or adjacent toat least one of the two middle incisors.
 17. The method of claim 1,further comprising: providing the delivery assembly with a deliverytube; and fluidly coupling the delivery tube to the reservoir and alsoto the delivery port so as to provide for fluid delivery of the non-gasliquid preparation of stimulant from the reservoir to the delivery port.18. The method of claim 1, further comprising: providing the dentalretainer tray as a palatal bridge-less tray with a dental cavityconfigured to receive and nest upon at least one tooth in the securedconfiguration; and nesting the dental cavity on at least one tooth inthe mouth in the secured configuration.
 19. The method of claim 1,wherein the stimulant comprises a cryogenic cooling stimulant.
 20. Themethod of claim 1, wherein the stimulant comprises a flavor.
 21. Themethod of claim 1, wherein the stimulant comprises a smell stimulantcomprising an odor.
 22. The method of claim 1, wherein the stimulantcomprises a liquid taste stimulant.